7th Scientific Meeting | June 16, 2017 - Manitoba Neuro · 2017-06-07 · neurosciences. MNN...

7th Scientific Meeting | June 16, 2017

Welcome message ......................................................................... 3

general InformatIon ...................................................................... 4

sponsors.................................................................................... 5

exhIbItor lIstIng.......................................................................... 6

about mnn................................................................................. 7

acknoWledgements......................................................................... 9 program..................................................................................... 10

keynote speakers.......................................................................... 13

speaker abstracts ........................................................................ 15

poster lIstIng ............................................................................ 20 poster abstracts ......................................................................... 24 author Index .............................................................................. 52

TABLE OF CONTENTS

3 7th Scientific Meeting

WELCOME

June 16, 2017

The Manitoba Neuroscience Network fosters inter-disciplinary fundamental and clinical neuroscience research and disseminates the progress of their constituents to the wider community.

We are pleased to announce our 2017 annual meeting. The theme of this year’s meeting is Brain Connections and Mental Health. Mental health includes our emotional, psychological and social well-being, and is an important factor affecting how we think, feel and act. The goal of this year’s meeting is to bring together researchers, clinicians and community stakeholders in discussing mental health research being conducted in our province and its impact on our communities.

In 2010, the Manitoba Neuroscience Network held its first scientific meeting of neuroscience faculty and trainees. Since then, the popularity of these annual meetings has continued to grow, drawing 150-200 attendees each year. We hope that this year’s annual meeting will build upon the achievements.

I’m excited to be the 2017 MNN Meeting Chair. This year’s meeting will feature two keynote speakers: Dr. Jeff Lichtman from Harvard University is a pioneer and world leader in the study of brain connectivity, and Dr. Jitender Sareen (Head of Psychiatry, University of Manitoba) is an internationally renowned expert in mental health research.This year’s meeting will also feature a special session “Science and Society; Collaborating for Change” which underscores MNN’s resolve to engage with the wider community.

We encourage you to register for this meeting to learn more about the research and opportunities in your community in a setting which encourages social interaction.

Thank you to all speakers, session chairs, and poster judges. Welcome to MNN 2017.

Sincerely,

Tabrez J. SiddiquiChair, 2017 MNN Scientific MeetingPrincipal Investigator, Neuroscience Research ProgramKleysen Institute for Advanced MedicineHealth Sciences Centre

Manitoba Neuroscience Network 2017 4

GENERAL INFORMATIONMEETING LOCATION

Radisson Hotel Winnipeg Downtown288 Portage AvenueWinnipeg, MB R3C 0B8

T: (204) 956-0410F: (204) 786-6588

Registration materials are available in the main conference foyer.

Main scientific sessions will be held in Ambassador A.

Poster displays will be held in Terrace East/Terrace West.

Exhibitor displays will be held as directed on site.

REGISTRATION AND INFORMATION: The registration desk will be open starting from 8:30 am on June 10th, and will be located in the main conference foyer. Your pre-paid registration material will be available from this desk. Conference information is also available at this location. A limited number of onsite registrations may be available. Please inquire. Note that the organizers cannot guarantee the availability of conference material for onsite registrants.

MEALS AND REFRESHMENTS: Coffee and snacks will be provided throughout the day. Lunch will also be provided. The afternoon poster session will be accompanied by hot appetizers. A cash bar service will also be provided during the poster session. If you have food allergy concerns, please notify attendants at the registration/information desk. All possible will be done to accommodate special requests.

POSTER INFORMATION:Poster presentations will take place as directed onsite. Poster board assignments were sent to registrants by e-mail. They are also available in the printed program or at the registration/information desk. Posters should be mounted before 9:00 am. The main poster viewing opportunity is between 4:30 and 6:30 pm, during the reception. There will also be opportunities to see posters during coffee and lunch breaks. Poster board sizes are 54” wide by 36” high. Materials for hanging posters will be provided onsite. The Winnipeg Chapter Society for Neuroscience takes no responsibility for posters remaining after 6:30 pm.


SPONSORS


EXHIBITOR LISTING

Please visit our exhibitors behind the registration desk, outside the main session room (Ambassador A)


ABOUT MNN

WHAT IS THE MANITOBA NEUROSCIENCE NETWORK?

The Manitoba Neuroscience Network (MNN) is an organization of academic faculty, physicians, research professionals and trainees dedicated to advancing networking, outreach and education in the neurosciences in Manitoba. Over 60 primary research investigators from four University of Manitoba Faculties, five research institutes and the University of Winnipeg are unified by the activities of the MNN in a virtual institute model, showcasing world-class interdisciplinary neuro-sciences research being conducted in Manitoba, recruiting and training highly qualified research personnel and creating new opportunities to inform the public of the value of research in the neurosciences.

MNN research is enabled by a tapestry of collaborations, leveraging diverse interdisciplinary strengths among faculty researchers. Collaborations are formed and nurtured by consistent MNN networking opportunities including the MNN Seminar and Speaker Series and the MNN Annual Scientific Meeting. MNN members are committed to research training in the neurosciences by offering a diverse range of graduate degree programs in the neurosciences, as well as awards for conference travel, distinguished speaker nominations and more through the University of Manito-ba, Faculty of Graduate Studies.

MNN outreach is accomplished by a rich and growing series of activities including extensive par-ticipation in International Brain Awareness Week, public presentations, Café Scientifique public forums on current topics, creation and curation of neurosciences-based art, and funding awards for aspiring research neuroscientists.

The MNN also operates a local chapter of the Society for Neuroscience (SFN). The SFN Winnipeg Chapter has a 30 year history as a vibrant SFN chapter with over 200 active members whose professional dues and volunteer commitments fuel opportunities for neuroscience networking, outreach and education, led by the Manitoba Neuroscience Network.


WHO’S INVOLVED?

GOVERNANCE:

President: Chris Anderson Professor of Pharmacology & Therapeutics University of Manitoba Director, Neuroscience Research Program Kleysen Institute for Advanced Medicine

Secretary: David McCrea Professor of Physiology & Pathophysiology Member, Spinal Cord Research Centre University of Manitoba Treasurer: Paul Fernyhough Professor and Head of Pharmacology & Therapeutics University of Manitoba Director, Division of Neurodegenerative Disorders St. Boniface Hospital Research Councilors: Phillip Gardiner Tammy Ivanco Brent Fedirchuk Vacant Vacant

OPERATIONS:

Chapter President/ Chris AndersonMNN Executive Director

Networking Director: Chris AndersonChair, Seminar Series: Eftekhar EftekharpourChair, 2017 Meeting: Tabrez SiddiquiMeeting Secretariat: Kelly Jorundson

Outreach Director: Sari HannilaChair, Promotions/Social Media: Crystal Acosta

Assistant (Networking): Kelly JorundsonAssistant (Outreach): Kae NormandeauAssistant (General): Sharon McCartneyAssistant (IT): Gilles Detillieux


ACKNOWLEDGEMENTS

SPECIAL THANKS TO:

MNN2017 - Nick Shepel Poster Awards

The fund was established by the Division of Neurodegenerative Disorders, St. Boniface Hospital Research Centre, to honor Nick Shepel who was an outstanding researcher, friend and leader. Nick was a true inspiration to his laboratory partners and brought fire, humor, and a desire to al-ways excel. His insistence to always try better has had a permanent effect on his lab mates and peers. Nick led by example and taught that detailed preparation and execution of experiments ensured reliable results.

This year, there will be two awards given for best posters.

MNN ORGANIZING COMMITTEEDr. Tabrez J. Siddiqui, Meeting Chair Dr. Chris Anderson, MNN PresidentKelly Jorundson, Meeting SecretariatKae Normandeau, Meeting Secretariat

VOLUNTEERS:Deb FowlerJessica Shieh


Friday, June 16th, 2017

8.30–5.00 Registration Desk Open

8.45–8.55 Opening Remarks

Dr. Tabrez SiddiquiChair - 2017 MNN Scientific MeetingPrincipal Investigator, Neuroscience Research Program, Kleysen Institute for Advanced Medicine, Health Sciences Centre; Assistant Professor of Physiology and Pathophysiology, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba

KEYNOTE SPEAKER: Dr. Jeff W. Lichtman

Chair: Dr. Chris AndersonDirector, Neuroscience Research Program, Kleysen Institute for Advanced Medicine, Health Sciences Centre; Professor, Department of Pharmacology & Therapeutics, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba

9.00–9.55 Does connectomics make sense Dr. Jeff W. Lichtman Jeremy R. Knowles Professor of Molecular and Cellular Biology, Harvard University; Ramón y Cajal Professor of the Faculty of Arts and Sciences, Harvard University

THEME: funDamentaL mechanisms

Chair: Dr. Michael Jackson Principal Investigator, Neuroscience Research Program, Kleysen Institute for Advanced Medicine, Health Sciences Centre; Assistant Professor, Department of Pharmacology & Therapeutics, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba

10.00–10.20 Placing the midline thalamus within the brain circuits that mediate emotions and SP-1 motivation Dr. Gilbert J Kirouac

Professor, Departments of Oral Biology and Psychiatry, Colleges of Dentistry and Medicine, Rady Faculty of Health Sciences, University of Manitoba

10.20–10.40 Coffee Break

10.45–11.05 Epigenetic control and mental health; Implicating the role of MeCP2 and DNA SP-2 Methylation in Rett Syndrome Dr. Mojgan Rastegar

Associate Professor, Department of Biochemistry and Medical Genetics, Regenerative Medicine Program, Rady Faculty of Health Sciences, Max Rady College of Medicine, University of Manitoba

10.45–11.05 Trainee Talk To be selected from submitted abstracts

PROGRAM


PROGRAM

SPECIAL SESSION: “science anD society; coLLaborating for change”

Chair: Dr. Jean Eric GhiaAssociate Professor, Departments of Immunology & Internal Medicine, University of ManitobaDirector, Gastrointestinal Basic Biology Research, IBD Clinical & Research Centre

11.20–11.35 MNN Outreach: Connecting Neuroscientists to the CommunitySP-3 Dr. Sari Hannila

Associate Professor, Department of Human Anatomy and Cell Science, Rady Faculty of Health Sciences, University of Manitoba

11.35–11.50 Looking back, moving forward a model of First Nation mental wellnessSP-4 Ms. Stephanie Sinclair

Graduate Student, Native Studies, University of Manitoba

11.50–12.05 Why we need to move beyond compliance to connectionSP-5 Ms. Deborah Dykstra

Co-founder of the Manitoba Association for Developmental Autism Programs and Therapies (ADAPT);Board member and certified trainer for The Manitoba Association for Universal Design for Learning (MAUDeL); Graduate Student in Inclusive Education at the University of Manitoba

12.05–12.20 All kinds of brains: Talking about neurodiversity in the communitySP-6 Ms. Lisa van den Hoven

Inspire Community Outreach Inc.

12.05–1.20 Lunch, Poster Viewing

KEYNOTE SPEAKER: Dr. JitenDer sareen

Chair: Dr. Tabrez Siddiqui

1.30-2.20 Posttraumatic stress disorders in adults Dr. Jitender Sareen

Professor and Head of Psychiatry, Professor of Psychology & Community Health Sciences, University of Manitoba; Medical Director and Head, WRHA Adult Mental Health Program; Director of Research and Anxiety Services, Group Leader, Manitoba Population Mental Health Research Group

THEME: cLinicaL

Chair, Dr. Tiina KauppinenPrincipal Investigator, Neuroscience Research Program, Kleysen Institute for Advanced Medicine, Health Sciences Centre, Assistant Professor, Department of Pharmacology & Therapeutics, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba

2.25-2.45 Abnormal connectivity patterns in Posttraumatic stress disorderSP-7 Dr. Ji Hyun Ko

Principal Investigator, Neuroscience Research Program, Kleysen Institute for Advanced Medicine, Health Sciences Centre; Assistant Professor, Department of Human Anatomy and Cell Science, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba


2.45-2.55 Coffee Break

2.50-3.20 Suicide: Epidemiology, risk assessment, and interventionSP-8 Dr. James Bolton

Associate Professor of Psychiatry, Psychology, and Community Health Sciences, University of Manitoba; Adjunct Scientist, Manitoba Centre for Health Policy

3.20–3.40 Transcranial Magnetic Stimulation in the Treatment of Obsessive-Compulsive SP-9 Disorder: Current Perspectives Dr. Mandana Modirrousta

Assistant Professor, Department of Psychiatry, University of Manitoba; Director, Neuromodulation and Neuropsychiatry Unit, University of Manitoba

3.40-3.50 Trainee talk to be selected from submitted abstracts

4.00-7.00 Poster session, social reception and awards ceremony

PROGRAM


Dr. Jeff W. Lichtman Jeremy R. Knowles Professor of Molecular and Cellular Biology, Harvard University;Ramón y Cajal Professor of the Faculty of Arts and Sciences, Harvard University

KEYNOTE SPEAKER

BIOSKETCH:Jeff W. Lichtman is Jeremy R. Knowles Professor of Molecular and Cellular Biology and the Ramón y Cajal Professor of the Faculty of Arts and Sciences at Harvard University. Lichtman is a developmental neurobiologist interested in the way in which experience alters nervous system organization in long lasting ways. He has participated in the development of a number of methods that describe neural connectivity at the level of individual synapses (connectomics) using fluorescence (e.g., Brainbow) and electron microscopical methods (e.g., ATUM). Lichtman graduated from Bowdoin College with a degree in Biology and from Washington University School of Medicine in 1980 with a Ph.D. in Neurobiology and a M.D. After postdoctoral work at Harvard Medical School, Lichtman joined the faculty of Washington University and remained there for twenty years before moving to his present position at Harvard in 2004. He is a member of the National Academy of Sciences.

RESEARCH INTERESTS:Lichtman’s research focuses on the study of neural connectivity and how it changes as animals develop and age. With his colleagues he has developed a number of tools that permit synaptic level analysis of neural connections. These include activity dependent uptake of fluorescent dyes, transgenic approaches to label individual nerve cells, and “combinatoric” methods (e.g., DiOlistics, Brainbow, and NPS) to label many nerve cells in the same tissue. In addition, he has helped develop automated electron microscopy approaches for large scale neural circuit reconstruction. These connectomic methods seek to make it routine to acquire neural circuit data in any nervous system. The central focus of his work is to describe the ways in which developing nervous systems change to accommodate information that is acquired by experience. Much of this work has centered on the mammalian peripheral nervous system which undergoes profound activity-dependent circuit reorganizations in early life. These alterations allow axons to prune most of their synaptic branches while strengthening a small subset of synapses in a competitive process called synapse elimination. Study of the dynamic changes that occur in circuits has required not only describing circuits in great detail at single time points but also visualizing how connections change over minutes, months and even years using in situ imaging approaches in living animals.


Dr. Jitender Sareen Professor and Head of Psychiatry, Professor of Psychology & Community Health Sciences, University of Manitoba; Medical Director and Head, WRHA Adult Mental Health Program; Director of Research and Anxiety Services, Group Leader, Manitoba Population Mental Health Research Group

KEYNOTE SPEAKER

Posttraumatic stress DisorDers in aDuLts

The presentation will provide:1) Epidemiology of Trauma and Posttraumatic Stress Disorder (PTSD).2) Describe the biopsychosocial risk and protective factors for the development of PTSD.3.) Describe general guidelines for the prevention, and treatment of PTSD.

BIOSKETCH:Dr. Sareen is a psychiatrist, professor, and head of the department of psychiatry at the University of Manitoba. He has over 20 years of experience providing cognitive behavioural therapy and received specialized training at the Beck Institute for Cognitive Behavior Therapy. Dr. Sareen has received funding to support his CBT work including a Manitoba Patient Access Network (MPAN) grant and a Worker’s Compensation Board of Manitoba Research and Workplace Innovation Program (RWIP) grant. He received awards for excellence in clinical research from the Canadian Psychiatric Association, Canadian Institutes of Military and Veterans Health Research Forum and the Academy of Cognitive Therapy. Dr. Sareen was also awarded the Manitoba Health Research Council Chair Award for Military Mental Health and Aboriginal Suicide Research, and has published over 280 articles in the areas of traumatic stress, anxiety disorders, aboriginal suicide, and military mental health.


SPEAKER ABSTRACTS

SP-1Dr. Gilbert J. KirouacProfessor, Departments of Oral Biology and Psychiatry, Colleges of Dentistry and Medicine, Rady Faculty of Health Sciences, University of Manitoba

PLacing the miDLine thaLamus Within the brain circuits that meDiate emotions anD motivationABSTRACT:My laboratory is interested in discovering how different regions of the brain function together to produce the behavioral actions associated with strong emotions. We focus on an area of the brain called the thalamus which is known to operate as a re-lay between different regions of brain that control emotions and motivation. We are trying to identify the connections and neurochemical substances between the thala-mus and other areas of the brain that translate the memories of events with strong emotional significance into actions related to these memories. We have identified a chemical signal in the thalamus of animals that contributes to the avoidance of risky situations following a strong fear-inducing situation. For example, a memory asso-ciated with painful experience may cause someone to avoid situations that resemble where the experience occurred. In some cases, the painful experience may gen-eralize leading to avoidance of circumstances that are far-removed from the actual experience. We hope that our research may result in new treatments to emotional disorders like generalized anxiety and post-traumatic stress disorder. Our research is also directed at understanding the brain mechanisms that produce addictive be-havior and other psychiatric disorders with dysregulation of emotions.

BIO:Dr. Kirouac is a professor in the Colleges of Dentistry and Medicine. He received an undergraduate degree in Psychology/Biology and a M.Sc. and Ph.D. in Anatomy from the University of Manitoba. He went on to complete post-doctoral work at the Western University in London Ontario and at the University of Calgary followed by a faculty position at the Memorial University of Newfoundland before returning to the University of Manitoba. Dr. Kirouac is interested in the brain mechanisms associated with emotions and motivation. His laboratory applies anatomical, electrophysiolog-ical, pharmacological, and molecular techniques to investigate how the brain pro-duces maladaptive behaviors like fear, anxiety and drug addiction. This involves the use of animal models of psychiatric disorders to identify these neural mechanisms. The purpose of this research is to provide a better understanding of how the brain regulates complex emotional behavior and to identify novel treatments for clinical disorders.


SPEAKER ABSTRACTS

SP-2Dr. Mojgan RastegarAssociate Professor, Department of Biochemistry and Medical Genetics, Regenerative Medicine Program, Rady Faculty of Health Sciences, Max Rady College of Medicine, University of Manitoba

ePigenetic controL anD mentaL heaLth; imPLicating the roLe of mecP2 anD Dna methyLation in rett synDromeEpigenetics regulate gene expression and brain development through mechanisms that are not directly controlled by genomic DNA sequences. Recent discoveries have highlighted the importance of epigenetic mechanisms in neuroscience and mental health. Perhaps one the best-studied types of epigenetic modifications is DNA meth-ylation. The regulatory role of DNA methylation is delivered through an orchestrated action of “readers”, “writers”, and “erasers” of DNA methylation. In the brain, the major DNA methylation reader that binds to, and interprets different types of DNA methylation is called “MeCP2”. In 1992, Dr. Adrian Bird and his team discovered MeCP2 as the prototype member of DNA methyl binding proteins. Seven years later, Dr. Huda Zoghbi and her group dis-covered that MECP2 gene mutations are the primary cause of Rett Syndrome (RTT). RTT is a severe neurodevelopmental disorder with a frequency of 1:10,000 live-birth females, without any cure. RTT patients seem to be normal at first, but by 6-18 months of age they display developmental regression, mental disability, neurological symptoms, seizers, speech deficiencies, irregular breathing, anxiety, and autism. It is well established that impaired protein translation is a characteristic of human RTT neurons. However, the underlying molecular mechanism of this phenotype is not fully understood. To study RTT pathobiology, my lab investigates the regulation and functional role of individual MeCP2 isoforms. In this regard, we aim to explain how MeCP2 mutations cause impaired protein translation in brain-derived neural stem cells, differentiated neurons and glia, as well as human RTT brain. Our recent results provide exciting new insight on how molecular deficiencies at the cellular and molec-ular levels lead to compromised brain function in RTT, and other MeCP2-associated brain disorders such as autism. My research program on MeCP2 isoforms and Rett Syndrome is currently supported by NSERC-Discovery Grant (2016-06035), International Rett Syndrome Foundation (IRSF) Basic Research Discovery Award (Award #3212), Ontario Rett Syndrome As-sociation (ORSA) Basic Discovery Award, and Children’s Hospital Research Institute of Manitoba (CHRIM) Operating Grant.


SPEAKER ABSTRACTS

SP-3Dr. Sari HannilaAssociate Professor, Department of Human Anatomy and Cell Science, Rady Faculty of Health Sciences, University of Manitoba

mnn outreach: connecting neuroscientists to the communityThe MNN sponsors a range of community outreach activities, including the Winnipeg Brain Bee, MNN Speaker’s Bureau, Cafe Scientifique, and Neurocraft. The goals of these activities are to enhance public awareness of neuroscience research and to provide youth with educational opportunities in neuroscience. In this presentation, MNN Director of Outreach, Dr. Sari S. Hannila, will describe the MNN’s outreach pro-gram, which was recently recognized with the CAN Advocacy and Outreach Award for Best Canadian SFN chapter.

SP-4Ms. Stephanie SinclairGraduate Student, Native Studies, University of Manitoba

Looking back, moving forWarD a moDeL of first nation mentaL WeLLnessThis presentation will review the components of mental wellness as identified by First Nations. The presentation will review models of wellness including First Nation strength based indicators, the Looking Back Moving Forward Model of Wellness, and the National First Nation Mental Wellness Continuum Framework. These models all discuss the importance of culture, language, balance and connection to the land. Mental wellness from an indigenous prospective is more than the treatment of men-tal illness, but rather a striving to achieve a Pimatisiwin, the “good life”.

SP-5Ms. Deborah DykstraCo-founder of the Manitoba Association for Developmental Autism Programs and Therapies (ADAPT); Board member and certified trainer for The Manitoba Association for Universal Design for Learning (MAUDeL); Graduate Student in Inclusive Education at the University of Manitoba

Why We neeD to move beyonD comPLiance to connectionInterventions for children with autism often focus on teaching information and be-haviours in a direct, repeatable way. But the problem for these students is really about coping - and thriving - with unpredictability and open-ended thinking. What happens if we are able to address these challenges in a collaboration-based ap-proach?


SP-6Ms. Lisa van den HovenInspire Community Outreach Inc.

aLL kinDs of brains: taLking about neuroDiversity in the communityThis short presentation will share the parent perspective of what it is like to raise a neurodiverse child, and make suggestions on how the neuroscience community can make a positive difference by supporting public education and informed choice for families.

SP-7Dr. Ji Hyun KoPrincipal Investigator, Neuroscience Research Program, Kleysen Institute for Advanced Medicine, Health Sciences Centre; Assistant Professor, Department of Human Anatomy and Cell Science, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba

abnormaL connectivity Patterns in Posttraumatic stress DisorDerPosttraumatic stress disorder (PTSD) is prevalent mental illness (~9% life-time) that results from exposure to trauma. As it is associated with vastly heterogeneous origins, accurate diagnosis and optimal treatment strategies are sometimes very dif-ficult to achieve. No known biomarker exists, which makes it difficult to assess treat-ment response and functional outcomes. Recent brain imaging studies have suggest-ed that PTSD mainly involves hyper-active limbic brain regions and mal-functioning top-down cognitive control of prefrontal cortices. We proposed a novel approach combining graph theory eigenvector centrality and principal component analysis to identify a disease-related covarying pattern of information flow in the context of brain network organization. Twenty two participants were scanned with functional magnetic resonance imaging (11 PTSD and 11 trauma-exposed comparison group; TEC). We have identified a spatial pattern of eigenvector centrality which was signifi-cantly increased in PTSD vs. TEC. The pattern was characterised by increased eigen-vector centrality in the orbitofrontal regions, amygdala, anterior cingulate, middle frontal and angular cortices. Interestingly, this pattern expression was significantly correlated with better memory performance for negatively vs. positively valenced items only in PTSD but not in TEC. The proposed analytic method may produce an objective neuroimaging-based biomarker for PTSD.

SPEAKER ABSTRACTS


SPEAKER ABSTRACTS

SP-8Dr. James BoltonAssociate Professor of Psychiatry, Psychology, and Community Health Sciences, University of Manitoba; Adjunct Scientist, Manitoba Centre for Health Policy

suiciDe: ePiDemioLogy, risk assessment, anD interventionSuicide is a leading cause of death around the world. Risk assessment is challenging for a variety of reasons, not least because conventional risk assessment approach-es rely on an individual’s self-report and some suicidal people may wish to conceal their plans. Service provision for suicidal patients is often substandard, particularly at times of highest need such as the time after discharge from hospital or the emer-gency department. A number of medication and psychotherapy-based treatments exist, however it remains unclear what are the best approaches to reduce suicide risk. Some of the most compelling evidence supports long established treatments such as lithium and cognitive behavioral therapy. Emerging options include ketamine and internet-based psychotherapies. This review will summarize the epidemiology of suicide, updates on the science of risk assessment, and will provide an overview of interventions shown to diminish suicide.

SP-9Dr. Mandana ModirroustaAssistant Professor, Department of Psychiatry, University of Manitoba; Director, Neuromodulation and Neuropsychiatry Unit, University of Manitoba

transcraniaL magnetic stimuLation in the treatment of obsessive-comPuLsive DisorDer: current PersPectivesEarly imaging studies highlighted the role of orbitofrontostriatal regions in obses-sive-compulsive disorder (OCD). More recent studies have uncovered other foci of abnormal activation in lateral frontal, anterior cingulate, middle occipital and pari-etal cortices, as well as the cerebellum. Cognitive neuroscience studies have shown impairment in implicit learning, response inhibition, attentional set shifting, and er-ror processing, suggesting that more distributed large-scale brain systems may be involved in OCD. The use of repetitive transcranial magnetic stimulation (rTMS) in treating several neuropsychiatric symptoms, including obsessive compulsive disor-der, has been increasingly investigated. By exerting a relatively focal effect and through the assumed neuroplasticity mechanism, rTMS has the potential to modulate the function of several brain networks. Recent meta-analysis studies have shown the overall efficacy of rTMS in the treatment of OCD symptoms compared to sham. These studies have so far used a variety of rTMS protocols involving different frequencies and stimulating different parts of the brain, including dorsolateral prefrontal cortex, anterior cingulate cortex, supplementary motor area, and of the brain, including dor-solateral prefrontal cortex, anterior cingulate cortex, supplementary motor area, and orbitofrontal cortex. This presentation will review the results of these randomized clinical trials and the applied rTMS protocols and will discuss the potential underlying cognitive mechanisms that are modulated by different rTMS approaches.


LISTING OF POSTER ABSTRACTSP # Presenter Authors & Affiliations Title

P-1 Scott Dyck [email protected]

S. M. Dyck, H. Kataria, K. T. San-thosh, B. Lang, J. Silver, and S. Karimi-Abdolrezaee

Pharmacological Inhibition of CSPGs Signaling Receptors Promotes a Pro-Regenerative Endogenous Re-sponse in Spinal Cord Injury.

P-2 Ghazaleh M. Shahriary [email protected]

G. M. Shahriary, H. Kataria, A. Alizadeh, K. T. Santhosh, and S. Karimi-Abdolrezaee

Neuregulin-1 plays a positive immu-nomodulatory role in demyelinating conditions

P-3 Audrey Katako [email protected]

A. Katako, P. Shelton, D. Levin, B. Bybel, M. Aljuaid, A. L. Goertzen, and J. H. Ko

A novel quantitative approach to positron emission tomography for the early diagnosis of Alzheimer’s disease

P-4 Mohamad-Reza Aghanoori [email protected]

M. Aghanoori, D. R. Smith, S. R. Chowdhury, M. G. Sabbir, N. A. Cal-cutt, and P. Fernyhough

Insulin prevents aberrant mitochon-drial phenotype in sensory neurons of type 1 diabetic rats

P-5 Aida Adlimoghaddam [email protected]

A. Adlimoghaddam, and B. C. Albensi Hyperammonaemia triggers inflam-matory responses in astroglial cells

P-6 Aida Adlimoghaddam [email protected]

A. Adlimoghaddam, R. S. Turner, and B. C. Albensi

Nilotinib enhances astroglial bioener-getics in Alzheimer’s disease

P-7 Jessica Jarmasz [email protected]

J.S. Jarmasz, D. Basalah, A. E. Chud-ley, J. R. Davie, M. Rastegar, M. R. Del Bigio

Prenatal alcohol affected epigenetic modifications in human and non-hu-man primate hippocampus

P-8 Jin Hee Kim [email protected]

J. H. Kim, L. Tessler, K. Braun, A. Rezaeian Mehrabadi, and T. M. Kaup-pinen

The role of microglial PARP-1 in cogni-tive impairments in offspring of dams with gestational diabetes

P-9 Jelena Djordjevic [email protected]

J. Djordjevic, S. R. Chowdhury, W. M. Snow, C. Perez, P. Fernyhough, and B. C. Albensi

Early mitochondrial deficits in the cortex of 3xTg female mice

P-10 Abrar Alhindi [email protected]

A. Alhindi, K. Solar, M. Aljuaid, D. E. Hobson, A. Borys, L. Ryner, C. R. Figley, and J. H. Ko

Functional connectivity of the caudate nucleus is correlated with cognitive performance in Parkinson’s disease

P-11 Katrina Armstrong [email protected]

K. Armstrong, M. Nazzal, X. Chen, K. Stecina, and L. Jordan

Chemogenetic activation of parapyra-midal brainstem neurons to evaluate motor consequences

P-12 Shubhamsingh Tanwar [email protected]

S. Tanwar, N. Lavine, and M. F. Jack-son

Mechanism of pannexin channel mechanosensitivity

P-13 Hardeep Kataria [email protected]

H. Kataria, A. Alizadeh, G. M. Shahri-ary, S. S. Rizi, R. Henrie, K. T. San-thosh, and S. Karimi-Abdolrezaee

Neuregulin-1 promotes oligoden-drogenesis and remyelination after lysolecithin-induced demyelination in the rat spinal cord

P-14 Abbas Rezaeian Mehrabadi [email protected]

A. Rezaeian Mehrabadi, J. H. Kim, G. Odero, L. Tessler, T. M. Kauppinen

The role of Microglial PARP-1 in Alz-heimer’s disease

P-15 Kevin Solar [email protected]

K. Solar, J. Kornelson, S. M. Courtney, and C. R. Figley

Relationships between structural and functional connectivity throughout large-scale human brain networks

P-16 Tracie Parkinson [email protected]

T. D. Parkinson, J. Kornelsen, and S. D. Smith

Default mode network activation pat-terns and the Five Facet Mindfulness Questionnaire (FFMQ)

P-17 Yiran Wang [email protected]

Yiran Wang, Y. Wang, H. Tan, and J. Wang

The regulation of thioredoxin anti-oxidant system in amyloid precursor protein/ presenilin 1 transgenic mice


LISTING OF POSTER ABSTRACTSP-18 Mamneet (Sheena) Manghera

[email protected]. Manghera, J. Ferguson-Parry, and R. N. Douville

Neuronal ERVK protein deposition in ALS: An aspect of TDP-43 misregula-tion

P-19 Ping Lu [email protected]

P. Lu, A. Kamboj, S. R. Chowdhury, P. Fernyhough, and C. M. Anderson

Poly(ADP-Ribose) polymerase-1 caus-es mitochondrial respiratory dysfunc-tion by regulating PGC-1α

P-20 Veni Bharti [email protected]

V. Bharti, and J. Wang The effect of antidepressants on the thioredoxin system

P-21 Lingling Lu [email protected]

L. Lu, P. Lu, and C. M. Anderson Oxygen-glucose deprivation reduces cortical arteriole lumen diameter by generating 20-hydroxyeicosatetrae-noic acid

P-22 Harish Gangadharappa [email protected]

H. Gangadharappa, N. Lavine, M. L. Johnston, J. C. Belrose, F. Caetano, J. F. MacDonald, and M. F. Jackson

Regulation of TRPM2 channels by Fyn kinase: Implications for Alzheimer’s disease

P-23 Albert Yeung [email protected]

A. Yeung, Y. Xie, N. Lavine, and M. F. Jackson

Contribution of Pannexin-1 activation to amyloid-beta induced synaptotox-icity and neurotoxicity

P-24 Sheryl Herrera [email protected]

S.L. Herrera, M. E. Mercredi, R. Buist, K. M. Matsuda, and M. J. Martin

Inferring axon diameters in the hu-man corpus callosum

P-25 Brent Aulston [email protected]

B. Aulston, G. L. Odero, and G. Glaz-ner

Secreted Amyloid Precursor Protein alpha prevents aberrant tau phos-phorylation and unfolded protein response activation in the cortices of diabetic mice

P-26 Dali Zhang [email protected]

D. Zhang, A. Katako, S. Li, G. J. Kir-ouac, and J. H. Ko

The effect of levodopa dosage and duration on the progression of levodo-pa-induced dyskinesia in a rat model of Parkinson’s disease

P-27 Xiaodan Jiao [email protected]

X. Jiao, N. Ashtari, M. Rahimi-Balaei, and H. Marzban

The sonic hedgehog signaling path-way in development of cerebellar granule cells

P-28 Morgan Mercredi [email protected]

M. E. Mercredi, S. L. Herrera, R. Buist, K. M. Matsuda, and M. J. Martin

Toward a clinical measurement of axon diameters in the human corpus callosum

P-29 Chetan Patil [email protected]

C. Patil, N. Lavine, and M. F. Jackson Mechanism of pannexin channel acti-vation in Alzheimer’s disease

P-30 Prajwal Raghunatha [email protected]

P. Raghunatha, L. Tessler M. Steven-son, M. F. Jackson and T. M. Kauppin-en

Role of TRPM2 in microglial activation outcome

P-31 Maram Aljuaid [email protected]

M.Aljuaid, D. E. Hobson, A. Borys, K. Williams, A. Katako, T. Chung, L. Ryner, A.L. Goertzen, and J. H. Ko

A novel quantitative method of pre-dicting levodopa induced dyskinesia in Parkinson’s disease

P-32 Maryam Rahimi-Balaei [email protected]

M. Rahimi-Balaei, N. Ashtari, X. Jiao, and H. Marzban

The role of a novel subset of mesen-cephalic neural crest derived cells in cerebellar nuclei development in mice

P-33 Christopher Hart [email protected]

C. G. Hart, S. M. Dyck, H. Kataria, K. T. Santhosh, S. Karimi-Abdolrezaee

Elucidating the role of bone morpho-genetic protein 4 in endogenous cell response and astrocyte reactivity following spinal cord injury


LISTING OF POSTER ABSTRACTSP-34 Xiaoyu Chen

[email protected]. Chen, P. Bhullar, K. Armstrong, M. Nazzal, and K. Stecina

Selective expression of designer receptors exclusively activated by designer drugs (DREADDs) in thora-co-lumbar cholinergic interneurons in genetically modified mice

P-35 Gurjit Nagra [email protected]

G. Nagra, X. Mao, and M. R. Del Bigio Pathogenesis of childhood ataxia with central nervous system hypomyelin-ation

P-36 Arsalan Alizadeh [email protected]

A. Alizadeh, S. M. Dyck, H. Kataria, D. Nguyen, K. T. Santhosh, and S. Karimi-Abdolrezaee

Neuregulin-1 positively modulates gli-al response and improves neurological recovery following traumatic spinal cord injury

P-37 Reiko Roppongi [email protected]

R. T. Roppongi, S. Dhume, K. Cham-pagne-Jorgensen, Y. Wang, T. J. Siddiqui

Regulation of a synaptic pathway in autism spectrum disorders

P-38 Thatchawan Thanasupawat [email protected]

T. Thanasupawat, S. Natarajan, A. Rommel, A. Glogowska, H. Bergen, J. Krcek, M. Pitz, J. Beiko, I. M. Verma, S. Ghavami, T. Klonisch, and S. Hom-bach-Klonisch

Dovitinib enhances temozolomide efficacy in glioblastoma

P-39 Prabhpal Kaur Bhullar [email protected]

P. K. Bhullar, B. Lynn, J. I. Nagy, and K. Stecina

Role of Cx36 proteins in peripheral nerves during the triple response and pain

P-40 Shreya Dhume [email protected]

S. Dhume, and T. J. Siddiqui LRRTM1 and LRRTM2 regulate circuit specific synapse development and behaviour

P-41 Xinwen Dong [email protected]

X. Dong, S. Li, and G. J. Kirouac Collateralization of projections from the paraventricular nucleus of the thalamus to the nucleus accumbens, bed nucleus of the stria terminalis, and central nucleus of the amygdala

P-42 Md Nasir Uddin [email protected]

M. N. Uddin, S. M. Courtney, and C. R. Figley

Optimized T2-weighting for gradient and spin echo (GRASE) based T1w/T2w MRI ratio mapping in human brain

P-43 Adam Hogan-Cann [email protected]

A. Hogan-Cann, L. Lu, A. Globa, S. Bamji, J. I. Nagy and C. M. Anderson

Endothelial NMDA receptors are in-volved in astrocyte-mediated cortical vasodilation

P-44 Matthew Martin [email protected]

M. J. Martin, and S. A. Booth Development of a reporter system allowing real-time monitoring of neu-rodegeneration in Prion disease

P-45 Crystal Acosta [email protected]

C. Acosta, C. M. Anderson, and H. D. Anderson

Characterization of vascular mor-phology and mechanical properties of middle cerebral arteries in hyperten-sive rats at risk for heart failure

P-46 Shayan Amiri [email protected]

S. Amiri, K. Curtis, C. O. Olson, M. R. Del Bigio, W. Xu, G. Hicks, J. R. Davie, and M. Rastegar

Investigating diagnostic biomarkers of fetal alcohol spectrum disorders (FASD) using embryonic alcohol ex-posure in differentiating neural stem cells

P-47 Shahla Shojaei [email protected]

S. Shojaei, J. Alizadeh, J. Thliveris, N. Koleini, E. Kardami, S. Hombach-Klo-nisch, T. Klonisch, and S. Ghavami

Involvement of autophagy in in-creased temozolomide-induced apop-tosis by the addition of simvastatin in glioblastoma cells


LISTING OF POSTER ABSTRACTSP-48 Pandian Nagakannan

[email protected]. Nagakannan, and E. Eftekharpour Oxidative modification of lysosomal

enzymes holds the key in cross-talk between protective autophagy and apoptotic cell death

P-49 Marina Mostafizar [email protected]

M. Mostafizar, and S. Katyal Enhancing chemotherapeutic respons-es in CNS malignancy through sup-pression of hyperactive DNA damage repair pathways

P-50 Benyamin Karimi [email protected]

B. Karimi, and T. J. Siddiqui Characterization of a neural circuit in a mouse model of schizophrenia

P-51 Amrit Boese [email protected]

A. S. Boese, A. Patterson, K. J. Man-guiat, A. Majer, and S. A. Booth

The regulation of NMDAR and mGluR5 by microRNA-128-3p with relevance to neurodegenerative disease

P-52 Brian Lithgow [email protected]

B. Lithgow Menstrual cycle mood changes detect-ed within EVestG recordings


POSTER ABSTRACTS

P-1 pharmacologIcal InhIbItIon of cspgs sIgnalIng receptors promotes a pro-regeneratIve en-dogenous response In spInal cord Injury.

S. M. Dyck*1, H. Kataria1, K. T. Santhosh1, B. Lang2, J. Silver2, and S. Karimi-Abdolrezaee1 1Department of Physiology & Pathophysiology, the Regenerative Medicine Program, the Spinal Cord Research Centre, University of Manitoba; 2Department of Neuroscience, Case Western Reserve University School of Medicine [email protected]

Traumatic spinal cord injury (SCI) results in significant cell death in myelin forming oligodendrocytes leading to demyelination and functional deficits. Resident multipotent neural stem/progenitor cells (NPCs) in the spinal cord have a tremendous potential to replace lost oligodendrocytes following SCI. However, the ability of NPCs to proliferate and differentiate into oligodendrocytes is challenged in the post-SCI microenvironment. We previously identified for the first time that injury-induced upregulation of chondroitin sulfate proteoglycans (CSPGs) is an underlying cause of this limitation. CSPGs inhibit several properties of NPCs including their survival, proliferation and differentiation. Using genetic silencing studies, we identified that CSPGs mediate their inhibitory effects through LAR and PTPσ receptors and deactivation of Erk1/2 and Akt pathways in NPCs. Our goal in the present study was to evaluate the therapeutic efficacy of two functionally blocking peptides against LAR (Intracellular LAR Peptide, ILP) and PTPσ (Intracellular Sigma Peptide, ISP) in promoting endogenous cell response after SCI. Using complimentary in vitro approaches, we show that ILP and ISP efficiently blocks CSPGs inhibitory effects on NPC attachment, survival, proliferation, and oligodendrocyte differentiation. In a clinically-relevant model of compressive SCI in rats we delivered ISP/ILP locally to the injured spinal cord to evaluate their potential therapeutic benefit. We conducted western blotting and immunohistochemical analyses to determine the effects of ILP and ISP therapy on glial scar formation, inflammation and oligodendrocyte preservation and replacement at various time points following injury. We find that perturbing LAR and PTPσ with ILP and ISP treatment limits oligodendrocyte apoptosis and myelin damage while increasing the ability of endogenous precursor cells for oligodendrogenesis at the expense of astrocyte differentiation. PTPσ and LAR control oligodendrogenesis partly by modulating microglia responses and RhoA activity. Inhibition of PTPs and LAR signaling is sufficient to foster a phenotype shift in microglia from a pro-inflammatory M1 to a pro-regenerative M2 that then activate an interleukin-10 mechanism leading to improved oligodendrogenesis in NPCs. Thus, our findings identify PTPσ and LAR as novel negative regulators of cell replacement in SCI, and suggest the potential of their modulation as a new viable target for enhancing immune response and endogenous repair process in the injured spinal cord. Supported by grants from CHN and NSERC.

P-2 neuregulIn-1 plays a posItIve Immunomodulatory role In demyelInatIng condItIons

G. M. Shahriary*, H. Kataria, A. Alizadeh, K. T. Santhosh, and S. Karimi-Abdolrezaee Regenerative Medicine Program, Department of Physiology and Pathophysiology, University of Manitoba [email protected]

Activation of resident microglia in concert with infiltrating leukocytes initiate a pro-inflammatory process that plays pivotal role in oligodendroglial death and myelin damage in demyelinating conditions such as spinal cord injury and multiple sclerosis. We have shown that the neuronally-derived growth factor, neuregulin-1 (Nrg-1), is acutely downregulated in demyelinating lesions. Our goal in this study was to unravel the ramification of Nrg-1 decline on immune response using in vitro and in vivo models. Primary microglia were harvested from rat cerebral cortex and cultured in DMEM-Ham’s F12 containing 10% FBS. Lipopolysaccharide (LPS) was used to activate cells. The cells were treated with recombinant human Nrg-1β1 (rhNrg-1β1) for 72 hours. For in vivo studies, lysolecithin (LPC) was injected into the rat spinal cord to induce focal demyelination. We delivered rhNrg-1β1 intraspinally at the time of LPC injections using poly lactic-co-glycolic acid (PLGA) microparticles for 7 and 14 days. We used immunohistochemistry and western blotting to analyze inflammatory response at different time-points after LPC injection. Our in vitro assays demonstrated a significant reduction in the secretion of pro inflammatory cytokine, Interleukin-1β, and nitric oxide from activated microglia treated with Nrg-1. Our in vivo studies in LPC-demyelinating lesion also showed that Nrg-1 promoted an anti-inflammatory phenotype in microglia and T cells characterized by increased expression of IL-10, FoxP3 and CD4. In conclusion, we demonstrate that Nrg-1 is a positive regulator of neuroinflammation seemingly through IL-10 dependent mechanisms. IL-10 is a key pro-regenerative factor that supports oligodendrocyte differentiation and myelin repair in CNS injury. Hence, Nrg-1 may constitute a beneficial therapy with immunomodulatory and regenerative roles in demyelinating conditions. Supported by CIHR, MS Society of Canada and Research Manitoba Institute.


POSTER ABSTRACTS

P-3 a novel quantItatIve approach to posItron emIssIon tomography for the early dIagnosIs of alzheImer’s dIsease

A. Katako*1,2, P. Shelton3, D. Levin4, B. Bybel4, M. Aljuaid1,2, A. L. Goertzen4, and J. H. Ko1,2* 1Department of Human Anatomy and Cell Science; 2Neuroscience Research Program, Kleysen Institute for Advanced Medicine, Winnipeg Health Sciences Centre; 3Section of Neurology, University of Manitoba; 4Department of Radiolo-gy, University of Manitoba; 5Alzheimer’s Disease Neuroimaging Initiative (ADNI) database (adni.loni.usc.edu) [email protected]

Positron Emission Tomography (PET) with fluorodeoxyglucose (FDG) radiotracer has been widely used as a brain imaging technique to aid diagnosis of Alzheimer’s disease (AD). To reduce variability associated with subjective FDG-PET readings, we developed a quantitative FDG-PET reading method for early AD diagnosis. We applied scaled subprofile modeling (SSM), a principal component analysis (PCA) technique, and a machine learning approach to the publically available FDG-PET database provided by AD neuroimaging initiative (ADNI). We identified FDG-PET images of 94 patients with AD and 90 normal controls (NL; who did not develop AD in >3 years follow-up period). Twenty subjects from each group were randomly selected (training set) and SSM/PCA was performed to construct AD-related metabolic covariance pattern (ADRP). Optimal threshold for ADRP expression that results in maximum sensitivity × specificity was determined, then prospectively applied to the remaining AD (n=74) and NL (n=70) to classify them. Following 1,000 repetitions, 1,000 voting machines were constructed. The percentage of voting results was used to determine the group. During voting, patients included in the training set were excluded. This approach classified AD vs. NL with high sensitivity (=0.77) and specificity (=0.87). When applied to patients with late-stage mild cognitive impairment (L-MCI) with >3 years of follow-up period, it accurately classified AD converters (n=33) vs. non-converters (n=75) with low sensitivity (=0.58) and moderate specificity (=0.63). This voting approach was applied to MCI patients scanned with FDG-PET (follow-up period: 10-56 months) in our Health Science Centre from 2010-2012. Good sensitivity (=0.72) and specificity (=0.70) were achieved in predicting patients who converted to AD (n=20) vs. who did not (n=18). In conclusion, we demonstrated a good feasibility of the proposed automated FDG-PET reading method that can be implemented at regional PET centres.

P-4 InsulIn prevents aberrant mItochondrIal phenotype In sensory neurons of type 1 dIabetIc rats

M. Aghanoori*, D. R. Smith, S. R. Chowdhury, M. G. Sabbir, N. A. Calcutt, and P. Fernyhough Division of Neurodegenerative Disorders, St. Boniface Hospital Research Centre; Department of Pharmacology & Therapeutics, University of Manitoba [email protected]

Diabetic neuropathy affects approximately 50% of diabetic patients. There is down-regulation of mitochondrial gene expression and function in human biopsy material and in dorsal root ganglia (DRG) from animal models of type 1 and type 2 diabetes. We hypothesized that loss of direct insulin signaling in diabetes contributes to loss of mitochon-drial function in DRG neurons and to development of neuropathy. Sensory neurons obtained from age-matched adult control or streptozotocin (STZ)-induced type 1 diabetic rats were cultured with or without insulin before determining mitochondrial respiration and expression of mitochondrial respiratory chain and insulin signaling-linked proteins. For in vivo studies age-matched control, STZ-induced and insulin-implanted diabetic rats were maintained for 5 months and DRG then analyzed for respiratory chain mRNA and protein levels, and COX activity. Insulin (10nM) significantly (P<0.5) increased phosphorylation of Akt and P70S6K by 4-fold and neurite outgrowth by 2-fold in DRG cultures de-rived from adult control rats. Insulin also augmented the levels of selective mitochondrial respiratory chain proteins and mitochondrial bioenergetics parameters, with spare respiratory capacity increased by up to 3-fold (P<0.05), in control and diabetic rat DRG cultures. In vivo experiments showed insulin-implanted diabetic animals exhibited im-proved thermal sensitivity in the hind paw and had increased dermal nerve density compared to untreated diabetic rats, despite no effect on blood glucose levels. In DRG of diabetic rats there was suppressed expression of mitochon-drial respiratory chain proteins and COX activity that was corrected by insulin therapy. Insulin elevates mitochondrial respiratory chain protein expression and function in sensory neurons and this is associated with enhanced neurite outgrowth and protection against indices of neuropathy.


POSTER ABSTRACTSP-5 hyperammonaemIa trIggers Inflammatory responses In astroglIal cells

A. Adlimoghaddam*1,2, and B. C. Albensi1,2 1Department of Pharmacology & Therapeutics, University of Manitoba; 2St. Boniface Hospital Research [email protected]

Ammonia is a highly toxic product that causes (when systemic blood concentrations are elevated) multiple disturbing or even fatal effects. This includes changes in intracellular pH, disruption of the mitochondrial membrane potential, ATP depletion, and severe negative effects on the central nervous system in mammals. However, the effect of high ammonia concentrations (hyperammonaemia) in bioenergetic and neuroinflammatory processes is not well under-stood. In this study, we investigated the role of hyperammonaemia in bioenergetic and inflammatory processes. To this regard, we isolated astroglial cells from the cortex of 7 day old C57/BL6 (control) mice. Oxygen consumption rates (OCR) were measured in cell cultures with the Seahorse XF24 (Seahorse Bioscience) analyzer after a 24 hr. dose-dependent treatment with ammonia (1 mM-5 mM). Hyperammonaemic conditions did not alter mitochondrial function in cultured astroglial cells vs. untreated cells (*p<0.05, n=5). However, the expressions of mitochondrial protein subunits (Complex III and V) were significantly down-regulated in ammonia treated astroglial cells. Further, Western blot analysis show decreases in the protein expression level of transcription factor nuclear factor kappa B (NF-κB) p65/C-rel subunits, cAMP response element-binding protein (pCREB), and antioxidant manganese superox-ide dismutase (MnSOD) in hyperammonaemic astroglial cells. Together these results suggest that targeting inflam-matory mediators such as NF-κB subunits and pCREB or MnSOD could provide an effective strategy for the treat-ment of neurological abnormalities associated with elevated ammonia levels. Supported by NSERC, St. Boniface Research, Research Manitoba, and the Everett Endowment Fund.

P-6 nIlotInIb enhances astroglIal bIoenergetIcs In alzheImer’s dIsease

A. Adlimoghaddam*1,3, R. S. Turner2, and B. C. Albensi13 1Department of Pharmacolology & Therapeutics, University of Manitoba; 2Department of Neurology, Georgetown Uni-versity; 3St. Boniface Hospital Research [email protected]

Alzheimer’s disease (AD) is a progressive age-related neurodegenerative disease. Although neurofibrillary tangles (NFTs) and amyloid beta (AB) are well-established hallmarks of AD, the earliest deficits in the pathological progres-sion of AD seem to be caused by impaired mitochondrial function – well before the robust appearance of AB and NFTs. Our current understanding of AD proposes there are several etiopathogenetic mechanisms that can affect mitochondrial function that are associated with AD. In this study, we investigated the effect of the FDA-approved anti-cancer drug, Nilotinib, on mitochondrial function and evaluated mitochondrial protein subunit expression. As-troglial cells were isolated from cortex of C57BL/6 mice (background control) and 3xTg mice, a transgenic model of AD. Oxygen consumption rates (OCR) were measured in cell cultures with the Seahorse XF24 analyzer after a 24 hr. dose-dependent treatment with Nilotinib (10 nm-1 uM). Nilotinib increased both basal and maximal mitochon-drial function in cultured AD astroglial cells vs. untreated AD cells but not in control cells (*p<0.05, n=5). Further, Western blot results show increased expression levels of transcription factor nuclear factor kappa B (NF-κB) p50/p105 subunits, cAMP response element-binding protein (pCREB), and antioxidant manganese superoxide dismutase (MnSOD) in AD cells and NF-κB p50/p105 subunits and pCREB in control cells. Moreover, Nilotinib increased expres-sion of mitochondrial complex (I-V) protein subunits in 3xTg cells but not in control cells. These results highlight a putative role for Nilotinib in regulating astroglial bioenergetics in AD and suggest that energy metabolism may be crucial therapeutic target for preventing and treating AD. Supported by NSERC, St. Boniface Research, Research Manitoba, and the Everett Endowment Fund.


POSTER ABSTRACTS

P-7 prenatal alcohol affected epIgenetIc modIfIcatIons In human and non-human prImate hIppo-campus

J.S. Jarmasz*, D. Basalah, A. E. Chudley, J. R. Davie, M. Rastegar, M. R. Del Bigio Department of Human Anatomy and Cell Science, University of Manitoba [email protected]

Introduction: One of the major hypotheses addressing the adverse effect of alcohol on the developing brain relates to the ability of alcohol to cause epigenetic changes. Epigenetics is the study of heritable changes in gene expression that do not result in DNA sequence changes. Instead, DNA and its surrounding components (e.g. histones, chroma-tin) are reversibly modified in order to influence gene expression. Objective: Demonstrate that prenatal alcohol exposure (PNAE) causes abnormal epigenetic changes in human brain cells. Methods: Autopsy records at Health Sciences Centre (Winnipeg, MB) were retrospectively reviewed. PNAE and/or a Fetal alcohol spectrum disorder (FASD) diagnosis was identified in 174 human autopsy reports. Of these cases, 17 human hippocampal/medial temporal brain samples will be examined at an epigenetic level along with age, sex and post-mortem delay matched controls (n=17). Samples are split up into 2 age groups: fetuses (8) and infants (9). As a relative comparison, a PNAE Macaque Primate brain model (~4-6 months of age, N=12) developed by Clar-ren, Bowden and Astley will also be included in this study in order to identify epigenetic modifications truly affected by PNAE. Results: Using immunohistochemistry, both human and macaque primate hippocampus samples are stained with an-tibodies targeting 16 epigenetic modifications (4 DNA, 12 histone). Preliminary data in the PNAE Macaque brain tis-sues showed decreases in 7 (5mC, 5hmC, 5caC, H3K4me3, H3K27me3, H3K36me3, H3K9ac), increases in 2 (H4K-5ac, Total H4) and no effect in 2 (H3K27ac, H4K12ac) of the 13 epigenetic modifications assessed so far: Preliminary data in the PNAE Human autopsy brain tissue showed a decrease in 1 (H3K27me3), an increase in 1 (5hmC) and no effect in 2 (H3K4me3, H4K12ac) of the 4 epigenetic modifications assessed so far. Conclusion: This will be the first PNAE study to utilize human and non-human primate brain tissue for the analysis of epigenetic changes. Our findings will not only validate previous epigenetic findings in rodent models, it will also have the potential to identify diagnostic tools (biomarkers) for early identification of FASD if the modifications can also be detected in biological samples (e.g. saliva), which will allow for the provision of better care to affected children. Supported by LGA of Manitoba and CIHR.

P-8 the role of mIcroglIal parp-1 In cognItIve ImpaIrments In offsprIng of dams WIth gesta-tIonal dIabetes

J. H. Kim*, L. Tessler, K. Braun, A. Rezaeian Mehrabadi, and T. M. Kauppinen Department of Pharmacology & Therapeutics, University of Manitoba [email protected]

Gestational diabetes mellitus (GDM) is complication during pregnancy resulting elevated blood glucose and promote inflammatory responses. Prolonged inflammation can impair cognitive functions of the offspring. Our previous work has established that PARP-1 has a key role in regulation of microglia, the resident brain immune cells. We hypoth-esized that microglial PARP-1 ablation reduces neuroinflammation-driven pathological changes in developing fetal neuronal networks and rescues cognitive abilities of the offspring exposed to GDM. GDM was induced by exposing dams to diets high in fatty acids and sucrose (HFS) or healthy diet (Lean) 6 weeks prior and throughout their pregnancy. The assessments of 15-week old male offspring showed impaired memory and atypical explorative behaviour in wt GDM offspring, but not in GDM offspring with microglia-targeted (CD11b) PARP-1 depletion. Complementary in vitro assessment of microglia prepared from wt vs. PARP-1 KO offspring from GDM vs. Lean dams demonstrated hyper-reactivity in GDM cells, which was prevented by either PARP-1 depletion or inhi-bition. To further confirm that prolonged PARP-1-driven microglial inflammatory responses can affect cognition and behavior, lentivirus induced hippocampal transduction of constitutive microglial (Iba1) PARP-1 activation was seen to mimic the behavior and cognitive abilities and behavior of GDM offspring. In combine our data suggests that GDM induces PARP-1-driven chronic microglial pro-inflammatory responses re-sulting in cognitive impairments in the offspring brain. PARP-1 serves as a therapeutic target in prevention of behav-ior changes, and memory and learning impairments in GDM offspring. Supported by CHRIM, Research Manitoba, and HSC Foundation.


POSTER ABSTRACTSP-9 early mItochondrIal defIcIts In the cortex of 3xtg female mIce

J. Djordjevic*, S. R. Chowdhury, W. M. Snow, C. Perez, P. Fernyhough, and B. C. Albensi Department of Neurodevelopmental Disorders, St. Boniface Hospital Research (DND); Department of Pharmacology & Therapeutics, University of Manitoba [email protected]

Alzheimer’s disease (AD) is the most common late onset neurodegenerative disorder with indications that women are disproportionally affected. They are more likely to develop AD, and they show greater cognitive impairment than men. AD is characterized by progressive neuronal loss, especially in the cortex and hippocampus. Evidence suggests contributory or even causal roles for specific mitochondrial defects at early stages of AD. Mitochondrial function is closely related to its morphology, and recent reports suggest that mitochondrial fission and fusion are altered in AD. We hypothesized that dysfunctional processes in brain mitochondria contribute to AD at different points in disease progression in 3xTg female and male mice. Hippocampal and cortical mitochondria of 3xTg and control mice (2, 6 and 14 month-old) were analyzed for Complex I-dependent oxygen consumption rates (OCR) on the XF24 Analyzer. Western blotting was used to determine protein levels of Complex I-V subunits, mitofusin 2 (Mfn2) and dynamin-re-lated protein 1 (Drp1). OCR was significantly decreased in cortical mitochondria from female 3xTg mice as early as 2 months of age, and at 6 months in males. Hippocampal mitochondria showed decreased maximal respiration and spare respiratory capacity only in 14-month old 3xTg females. Deficits in Complex I and IV protein levels were ob-served in the cortical mitochondria of 6-month old 3xTg females but not in males. Decreases in Mfn2 in the cortical mitochondria from both female and male 3xTg (6 month old) coincided with an increased level of Drp1. Our study showed that the onset of mitochondrial deficits is region- and sex-dependent in 3xTg mice. Supported by Research Manitoba, Alzheimer Society of Manitoba, the St. Boniface Hospital Foundation, and the Ev-erett Endowment Fund.

P-10 functIonal connectIvIty of the caudate nucleus Is correlated WIth cognItIve performance In parkInson’s dIsease

A. Alhindi*, K. Solar, M. Aljuaid, D. E. Hobson, A. Borys, L. Ryner, C. R. Figley, and J. H. Ko Neuroscience Research Program, Kleysen Institute for Advanced Medicine, Winnipeg Health Sciences Centre; De-partment of Radiology, University of Manitoba; Section of Neurology, Department of Internal Medicine, University of Manitoba [email protected]

One of the earliest and most common symptoms of Parkinson’s disease (PD) is cognitive impairment. It ranges from mild cognitive impairment (MCI) to severe dementia. Studies showed that the caudate nucleus is most relevant to cognition. The objective of this pilot study was to investigate whether there is any correlation between MoCA scores (Montreal Cognitive Assessment) and the functional connectivity of the caudate and to compare this connectivity with the connectivity of normal subjects. Functional magnetic resonance images (fMRI) were obtained for 10 PD (PD-MCI=5, PD-non-MCI=5), and for 9 healthy controls (HC). Patients were on their clinically determined anti-par-kinsonian medication. PD patients were recruited from Winnipeg and HC subjects were recruited from Baltimore, and they underwent similar resting-state fMRI protocol with a different scanner. We examined the functional connectivity of the caudate and putamen using graph theory analysis. For each region, we calculated the mean of the between-ness centrality (BC) for each subject at 10 different costs ranging from 15-25%, correlated it with MoCA scores and compared it to HC. Firstly, we found that the BC of the right caudate nucleus was significantly correlated with MoCA scores (r = 0.717, n = 10, P = 0.02), while the left caudate and bilateral putamen did not show similar correlations. Secondly, a significant difference was observed across the 3 groups for BC in the right caudate (F2.16 = 4.5, P < .05), where only the PD-non-MCI’s BC was significantly elevated compared to the HC (p=0.048, post-hoc Bonferonni test). A similar group difference was not observed in the left caudate or bilateral putamen (p>0.2). This preliminary study suggests that the functional connectivity of the right caudate nucleus may serve as a quantifiable indicator for PD cognitive deficits and that it may be potentially a compensatory mechanism. Supported by Manitoba Medical Service Foundation, Natural Sciences and Engineering Research Council of Canada, Brain Canada, University of Manitoba, King Saud University, Riyadh, Saudi Arabia, and Saudi Arabian Culture Bureau in Canada. We thank the staff members of PET and MRI centers at Health Science Centre for data acquisition.


POSTER ABSTRACTSP-11 chemogenetIc actIvatIon of parapyramIdal braInstem neurons to evaluate motor consequences

K. Armstrong*, M. Nazzal, X. Chen, K. Stecina, and L. Jordan Department of Physiology & Pathophysiology, University of Manitoba [email protected]

Purpose: Several brainstem regions are necessary to provide transmission of a descending signal to motor networks within the lower limbs. The parapyramidal region (PPR) appears to play an important role in the transmission of a descending signal in the neonatal rat. However, the importance of this region in adult rats has not been studied in detail. The recent advent of DREADDs (Designer Receptors Exclusively Activated by Designer Drugs) has allowed for non-invasive in vivo manipulation of neurons. Using DREADDs, the PPR can be selectively activated its designer drug, clozapine-n-oxide (CNO) to investigate its role in motor activity. Methods: DREADDs were stereotaxically injected in the PPR using adeno-associated viral vectors – AAV-hSyn-DIO-hM3Dq (mutated human muscarinic G-protein coupled receptor-Gq) with an m-Cherry reporter protein. After a re-covery period to allow transfection, rats were tested in both voluntary (open field) and fictive locomotion to evaluate motor activation after administration of CNO. In acute experiments, rodents received surgery under isoflurane anes-thesia to allow for recording of electroneurograms (ENGs of the tibial (Tib) and the common peroneal (CP) nerves). The preparation was decerebrated to permit the study of direct effects of PPR neurons without contribution of higher brain centers. To reliably evoke fictive locomotion, metal electrodes were stereotaxically targeted in the MLR for electrical stimulation (10-100 μA, 10-40 Hz). Results: Immunohistochemical detection and fluorescence microscopy revealed the presence mCherry protein within the PPR, providing evidence for the feasibility of transfection of these rodents with the selected AAV viral vector. Open field showed increased instances of freezing and grooming after CNO. Locomotor parameters did not change significantly after CNO compared to saline injected controls. In acute experiments, changes were observed in MLR-induced fictive locomotion and spontaneous ENG activity. In four ani-mals, there was an increase in ENG activity occurring between 3-20 minutes after CNO injection (1 mg/kg). These effects decreased, and a recovery condition similar to control was observed after 40 minutes. Conclusions: DREADDs were successfully transfected within the PPR and confirmed by the presence of the mCherry reporter. Activation of these neurons was inconclusive in open field measures but may be due to confounding effects from higher brain centers. The acute decerebrate experiment demonstrates that DREADD activation of the PPR increases MLR-induced activity and spontaneous activity in all nerves recorded.

P-12 mechanIsm of pannexIn channel mechanosensItIvIty

S. Tanwar*, N. Lavine, and M. F. Jackson Neuroscience Research Program, Kleysen Institute for Advanced Medicine, Winnipeg Health Sciences Centre; Depart-ment of Pharmacology & Therapeutics, University of Manitoba [email protected]

Ischemic stroke driven cytotoxic edema expedites Pannexin-1 (Panx1) channel activation, facilitating chemotax-is-guided neuronal injury and death. Mechanisms underlying osmotic cell swelling induced Panx1 regulation are poorly understood. The objective here is to establish the contribution of F-actin and microtubules to swelling-induced augmentation of Panx1 channel activity in HEK293 cells stably expressing mouse panx1 (flag-mPanx1). In cells voltage-clamped at -60 mV, application of extracellular solution (ECS) with depreciating osmolarity induced a corre-sponding progressive magnification in Panx1 mediated currents. The effects of cytochalasin-D (CytD; F-actin depo-lymerizing drug) and nocodazole (NDZL; tubulin depolymerizing drug) were evaluated using immunofluorescence imaging and whole cell patch clamp recording. CytD not only inhibited the escalation in Panx1 channel response during osmotic cell swelling but also abated the basal channel activity [767 pA (control; n=7), 319 pA (treated; n=8)] indicating that F-acting contributes to cell swelling induced mechanosensitive as well as basal channel regu-lation. Tubulin disruption showed poor inhibition of channel activity augmentation during osmotic stress-induced cell swelling. Cells expressing Panx1 truncations at C-term (shown to interact with F-actin) further attest the decline in basal and stress-induced Panx1 mediated currents. To conclude, F-actin plays an important role in the augmentation of Panx1 channel activity during osmotic stress-induced cell swelling.


POSTER ABSTRACTS

P-13 neuregulIn-1 promotes olIgodendrogenesIs and remyelInatIon after lysolecIthIn-Induced demyelInatIon In the rat spInal cord

H. Kataria*, A. Alizadeh, G. M. Shahriary, S. S. Rizi, R. Henrie, K. T. Santhosh, and S. Karimi-Abdolrezaee Regenerative Medicine Program, Department of Physiology and Pathophysiology, University of Manitoba [email protected]

Oligodendroglial cell death and demyelination are hallmarks of central nervous system (CNS) injuries and multi-ple sclerosis resulting in axonal damage and functional impairments. Restoration of myelin sheath (remyelination) remains a major obstacle as the ability of endogenous neural precursor cells (NPCs) and oligodendrocyte progenitor cells (OPCs) for oligodendrocyte replacement is hindered in the unfavorable milieu of demyelinating conditions. Our recent evidence shows that Neuregulin-1 (Nrg-1), a critical growth factor for oligodendrocytes, is dysregulated in demyelinating lesions that may underlie the poor endogenous replacement of oligodendrocytes and remyelination. Currently the role of Nrg-1 in demyelinating conditions is largely undefined. Here, we have used in vivo and in vitro models to unravel the impact of Nrg-1 downregulation in CNS demyelinating lesions of the spinal cord. Methods: We employed an in vivo rat model of lysolecithin (LPC)-induced focal demyelination. Recombinant human Nrg-1β1 (rhNrg-1β1) was delivered intraspinally at the time of LPC injections using biodegradable poly lactic-co-gly-colic acid (PLGA) microcarriers for various times. Spinal cord tissues were analyzed with ELISA, Western blotting, slot blotting, immunohistology and electron microscopy at different time-points after LPC injections. For in vitro studies, we used brain derived primary rat NPCs to assess the role of Nrg-1 in oligodendrocyte differentiation and maturation. For myelination studies, rat dorsal root ganglion neurons (DRGs) were co-cultured with NPCs under con-trol or Nrg-1 treated conditions. Differentiation, maturation and myelination were analysed using immunocytochem-istry. Co-immunoprecipitation and Western blotting was performed to identify Nrg-1 mediated receptor activation involved in oligodendrocyte regulation. Results: Our in vivo findings show that rhNrg-1β1 treatment promotes oligodendrocyte generation and maturation in LPC induced demyelinating lesions. Additionally, Nrg-1 treatment accelerated remyelination and resulted in signifi-cant improvement in myelin thickness. This was partly due to an increase in Schwann cell mediated remyelination with Nrg-1 treatment in demyelinated lesions. Nrg-1 therapy also resulted in a significant reduction in the expression of scar associated chondroitin sulfate proteoglycans (CSPGs) that are known to inhibit remyelination. Our comple-mentary in vitro studies also provided direct evidence that Nrg-1 significantly increases of the differentiation of NPCs into myelin basic protein expressing oligodendrocytes and promotes overall myelination in DRG-NPC co-cultures. Mechanistically, we demonstrate that Nrg-1 specifically mediates it effects through ErbB2 and ErbB4 receptor activa-tion. Conclusions: Our work for the first time demonstrates the impact of Nrg-1 in promoting oligodendrocyte replace-ment, recruitment of myelinating cells and axonal remyelination in demyelinating lesions of the CNS. Thus, resto-ration of the deficient levels of Nrg-1 in demyelinating lesions is a vital approach for myelin repair. Supported by the CIHR, Research Manitoba, and Rick Hansen Institute.


POSTER ABSTRACTSP-14 the role of mIcroglIal parp-1 In alzheImer’s dIsease

A. Rezaeian Mehrabadi*, J. H. Kim, G. Odero, L. Tessler, T. M. Kauppinen Department of Pharmacology, University of Manitoba [email protected]

Alzheimer’s disease (AD) is a main cause of dementia. AD pathology includes Aβ accumulation, neuroinflammation and compromised BBB. Microglia, the brain immune cells, play a key role in neuroinflammation, which can promote neurodegeneration. Microglial release of trophic factors, phagocytose and synaptic pruning can support brain health. We hypothesize that poly(ADP-ribose) polymerase-1 (PARP-1) activation drives microglial pro-inflammatory func-tions, which can directly disrupt BBB integrity (in vitro) and promote AD pathological events accelerating disease progression (in vivo). The effect of primary murine microglia on astrocytes and brain endothelial cells was assessed in co-cultures. Aβ-stimulation of microglia induced release of NO and TNFα, triggered astroglial activation and reduced endothelial expression of tight junction proteins (TJPs) in a PARP-1 dependent manner. NO and TNFα stimulation of endothelial cells reduced expression of TJPs (ZO-1 and Occludin) and increased paracellular (FITC-dextran, IRDye) permeabili-ty. To study whether chronic pro-inflammatory microglial activation accelerates AD progression in 3xTg-AD mice, we performed hippocampus-injection with microglia-directed lentiviral construct of mutant PARP-1 “LV-PARP-1on”(LV-Iba1-mPARP-1-RFP), which transduces constitutively active PARP-1 expression in microglia. Mice injected with this LV-PARP-1on showed deficits in NOR test already at 4 months of age, whereas AD mice injected with the control LV showed memory deficits only after 5 months of age. Immunostaining of the post-mortem brains revealed that LV-PARP-1 on reduced BBB integrity and promoted other pathological aspect of AD. Our data demonstrates that microglial PARP-1 mediated pro-inflammatory responses can directly jeopardize BBB integrity and drive AD pathology. Supported by Alzheimer’s Society Canada and Research Manitoba.

P-15 relatIonshIps betWeen structural and functIonal connectIvIty throughout large-scale human braIn netWorks

K. Solar*1, J. Kornelsen1, S. M. Courtney2, and C. R. Figley1

1Department of Physiology and Pathophysiology, University of Manitoba; 1Department of Psychological and Brain Sciences, Johns Hopkins [email protected]

The structural connectivity (SC) of the human brain is defined by the white matter pathways that link inter- and intra-hemispheric regions of the brain and provide the electrochemical substrate for neural activity. Functional con-nectivity (FC) is defined by anatomically-distinct brain regions that share temporally-coherent neural activity; and the human brain is organized into distributed functional networks of regions that are associated with various cogni-tive, sensory, and motor processes. The relationships through which SC couples with FC within functional networks are largely unknown. Therefore, the objective of the current study was to systematically investigate SC-FC coupling within the connections of six well-established functional networks. Whole-brain functional and structural MRI data were acquired from 32 neurologically-healthy adults; where resting state fMRI was used to quantify FC between predefined regions, and diffusion tensor and myelin water imaging techniques were used to quantify SC in the un-derlying white matter between regions. We then assessed SC-FC relationships using linear correlation and regression analyses. We found that despite each functional connection within each network having a direct structural connec-tion, there was a low direct correspondence between SC and FC strength but high indirect correspondence. More-over, we found that when at least two network nodes were located in a rich club region in an SC-FC comparison, there was a greater probability that the relationship was significant. Overall, these findings help set an empirical foundation for the notion that SC can provide indirect (to partial- [sharing one node] and non- [sharing zero nodes] overlapping connections) and divergent (to multiple partial- or non-overlapping connections) support to FC through rich club facilitation. Supported by a Brain Canada Platform Support Grant, and a Natural Sciences and Engineering Research Council Dis-covery Grant and Graduate Studentship.


POSTER ABSTRACTS

P-16 default mode netWork actIvatIon patterns and the fIve facet mIndfulness questIonnaIre (ffmq)

T. D. Parkinson*, J. Kornelsen, and S. D. Smith Department of Psychology, University of Manitoba; Department of Psychology, University of Winnipeg [email protected]

Mindfulness has been described as an orientation of attention to the present moment, with curiosity, intention, open-ness, and compassion. Mindfulness may refer to a transient experience (state mindfulness) or a more permanent personality attribute (trait mindfulness). Researchers have been using neuroimaging techniques to gain insights into the neural substrates underlying both state and trait mindfulness. Our study examined whether differential patterns of neural activity could explain individual differences on a common measure of trait mindfulness, the Five Facet Mindfulness Questionnaire (FFMQ). Twenty-eight undergraduate students completed the FFMQ prior to entering an MRI scanner. After undergoing a structural MRI scan, participants completed a seven-minute resting-state functional MRI scan. Resting-state data were analyzed using an independent-components analysis (ICA); this analysis allowed us to identify regions of correlated brain activity (i.e., resting-state networks). When examining the default mode network (DMN), we found that functional connectivity in the right anterior cingulate cortex was positively correlated with mindfulness scores. This region has been associated with resilience during emotion processing and suggests that mindfulness is associated with enhanced emotional regulation. Trait mindfulness was negatively correlated with functional connectivity in the middle temporal gyri, right superior frontal gyrus, and left middle frontal gyrus. These regions of the DMN are associated with introspective thought and mind-wandering. These results are consistent with the hypothesis that trait mindfulness is associated with less evaluation of emotional experiences and greater ability to reappraise negative stimuli.

P-17 the regulatIon of thIoredoxIn antIoxIdant system In amyloId precursor proteIn/ presenIlIn 1 transgenIc mIce

Yiran Wang*, Y. Wang, H. Tan, and J. Wang Department of Pharmacology & Therapeutics, University of Manitoba [email protected]

Alzheimer’s disease is a type of dementia that causes impairment of memory, thinking and behaviours, and is char-acterized by extracellular deposition of β-amyloid (Aβ) and intracellular neurofibrillary tangles. Many studies have consistently shown that Aβ induces oxidative stress, contributing significantly to neurodegeneration in Alzheimer’s disease. Thioredoxin (Trx) is a major oxidoreductase and inhibits oxidative stress by reversing protein cysteine oxidative modification and scavenging peroxides. Thioredoxin-interacting protein (Txnip), as an endogenous inhibi-tor, binds to Trx and inhibits Trx activity. In the present study, we examined protein levels of Trx and Txnip in brain of amyloid precursor protein/presenilin 1 (APP/PS1) double transgenic mice and primary cultured mouse cerebral cortical cells. We found that Trx is not significantly changed in brain of APP/PS1 mice. Although Txnip protein levels were not changed in hippocampus and frontal cortex of 3 and 6 month old APP/PS1 mice, Txnip protein levels were significantly increased in hippocampus and frontal cortex of 9 and 12 month old APP/PS1 mice. Further Aβ treatment also increased Txnip protein levels in primary cultured mouse cerebral cortical cells. It is interest in cultured cells that Trx protein levels were increased by treatment with Aβ for one day, but decreased by treatment with Aβ for 7 days. Our studies suggest that Aβ-upregulated Txnip may mediate Aβ-induced oxidative stress and that Txnip may be a potential target for treatment of Alzheimer’s disease. Supported by a Discovery Grant from Natural Sciences and Engineering Research Council of Canada (NSERC).


POSTER ABSTRACTSP-18 neuronal ervk proteIn deposItIon In als: an aspect of tdp-43 mIsregulatIon

M. Manghera*, J. Ferguson-Parry, and R. N. Douville Department of Biology, University of Winnipeg; Department of Immunology, University of Manitoba [email protected]

Retroviral sequences, such as human endogenous retrovirus-K (ERVK), comprise over 8% of our DNA. Enhanced expression of ERVK proteins contributes to neuronal damage in Amyotrophic Lateral Sclerosis (ALS). Majority of pa-tients with ALS also exhibit neuronal TDP-43 protein misregulation and aggregation, partly due to impaired ubiquitin proteasome system, autophagy and stress granule pathways. But, whether dysregulation of TDP-43 and protein quality control systems impacts ERVK proteostasis remains unexplored. Thus, we sought to evaluate whether wild-type and mutated TDP-43, and select protein clearance pathways, influence neuronal ERVK protein deposition in ALS. Human astrocytic SVGA cells and human neurons derived from ReNcell CX neural progenitors were transfected with wild-type or mutated TDP-43 plasmids. Cells were also treated with the pro-inflammatory cytokine TNFα and/or MG132, a proteasomal inhibitor and an autophagy enhancer. Using western blot and confocal microscopy, we show that over-expression of ALS-associated aggregating forms of TDP-43, but not wild-type TDP-43, significantly en-hanced ERVK viral protein accumulation. During inflammation and proteasome inhibition, astrocytes, but not neu-rons, were able to clear excess ERVK proteins through stress granule formation and autophagy. Through immunohis-tochemistry of autopsy motor cortex tissues, we confirmed that cortical neurons of patients with ALS failed to clear ERVK protein deposition despite evidence of enhanced stress granule and autophagic response. This highlights how multiple cellular pathways, in conjunction with disease-associated mutations, can converge to modulate the expres-sion and clearance of ERVK products. In ALS, ERVK protein aggregation is a novel aspect of TDP-43 misregulation contributing towards neuropathology. Supported by CFI, MMSF, CIHR, Research Manitoba, ALS Association, and University of Winnipeg

P-19 poly(adp-rIbose) polymerase-1 causes mItochondrIal respIratory dysfunctIon by regulatIng PGC-1α

P. Lu*, A. Kamboj, S. R. Chowdhury, P. Fernyhough, and C. M. Anderson Department of Pharmacology & Therapeutics, University of Manitoba [email protected]

Excitotoxic oxidative stress and DNA damage causes excessive activation of the nuclear enzyme poly(ADP-ribose) polymerase-1 (PARP-1). This leads to mitochondrial dysfunction and neuron death, but the mechanisms of PARP-1-induced mitochondrial damage are poorly understood. Peroxisome proliferator-activated receptor gamma coactiva-tor-1α (PGC-1α) is a master regulator of mitochondrial biogenesis and respiration. PGC-1α activity is influenced by sirtuins, which are nicotinamide adenine dinucleotide (NAD+)-dependent class III histone deacetylases. Since PARP-1 consumes NAD+, we hypothesized that PARP-1 leads to mitochondrial dysfunction in neurons by inhibiting sirtuin activity and preventing support of mitochondrial function by PGC-1α. Primary cortical neuron cultures were exposed to the DNA alkylating agent, N-methyl-N’-nitro-N-nitrosoguanidine (MNNG) to initiate pathological PARP-1 activa-tion. A Seahorse Flux Analyzer was then used to assess several facets of mitochondrial function. Beginning 4 hr after MNNG exposure, maximal respiratory rate, respiratory control ratio, and spare respiratory capacity were significantly reduced in a manner partially restored by PARP-1 inhibition (PJ34, 10 µM), PARP-1 deletion (parp-1-/- mice) or ex-ogenous replenishment of NAD+. MNNG caused PARP-1-dependent depletion of NAD+ levels and commensurate in-hibition of sirtuin deacetylase activity. Increased PGC-1α acetylation was also observed, corresponding with reduced PGC-1α binding to nuclear respiratory factor-1 (NRF-1), NRF-1 association with mitochondrial transcription factor A (TFAM) promoter, and TFAM expression. In agreement, mitochondrial DNA copy number and total mass were sig-nificantly attenuated by MNNG by a mechanism sensitive to PJ34 or exogenous NAD+ replacement. Taken together, these data demonstrate that PARP-1 activation causes NAD+ depletion severe enough to inhibit PGC-1α-directed mitochondrial mass and respiratory capacity in neuron cultures. Supported by Research Manitoba and the Winnipeg Health Sciences Center.


POSTER ABSTRACTSP-20 the effect of antIdepressants on the thIoredoxIn system

V. Bharti*1,2, and J. Wang1,2 1Neuroscience Research Program, Kleysen Institute for Advanced Medicine, Winnipeg Health Sciences Centre; 2De-partment of Pharmacology & Therapeutics, University of Manitoba [email protected]

Introduction: Antidepressants are the medications that are used to treat major depressive disorder (MDD). Although short term treatment with antidepressants increases monoamines in brain, but in clinical condition it takes almost 4-6 weeks for a depressed patient to stabilize the mood. The exact mechanism behind the lag phase between ad-ministration of antidepressants and clinical signs of improvement is not known yet. Studies have indicated that oxi-dative stress underlies the pathophysiology of MDD. Oxidative stress is the imbalance between reactive oxygen and nitrogen species produced as a byproduct of our metabolism and endogenous antioxidants of the body to combat this stress. Oxidation of cysteine by reactive oxygen and nitrogen species lead to reversible cysteine sulfenylation and nitrosylation respectively. Thioredoxin as an oxidoreductase can reverse cysteine sulfenylation and nitrosylation. Methods and Results: Using immunoblotting analysis, we have found that chronic treatment with antidepressants namely venlafaxine, desipramine and fluoxetine for 5 days significantly increased protein levels of thioredoxin in culture HT22 mouse hippocampal cells. Using biotin switch and dimedone methods, we also found that chronic treat-ment with stress hormone corticosterone for 5 days increased cysteine sulfenylation and nitrosylation in HT22 cells, while chronic antidepressant treatment significantly inhibited corticosterone-increased cysteine sulfenylation and nitrosylation. Conclusion: Our findings suggest that antidepressants inhibit cysteine oxidation by upregulating thioredoxin system. Supported by discovery grant, NSERC.

P-21 oxygen-glucose deprIvatIon reduces cortIcal arterIole lumen dIameter by generatIng 20-hy-droxyeIcosatetraenoIc acId

L. Lu*, P. Lu, and C. M. Anderson Neuroscience Research Program, Kleysen Institute for Advanced Medicine, Winnipeg Health Sciences Centre [email protected]

Brain ischemia and reperfusion is associated with secondary neuronal death resulting from prolonged regional hy-poperfusion, in part mediated by constriction of arterioles and capillaries. The mechanisms behind ischemic constric-tion are not clear but it was recently shown that brain slice capillaries constrict in response to simulated ischemia without reperfusion, in a manner dependent on pericyte contraction and death. We hypothesized that brain ischemia also constricts pre-capillary arterioles in a manner dependent on shifted balances of arachidonic acid (AA) metabo-lites. Acute cortical slices were exposed to oxygen-glucose deprivation (OGD) and analyzed by two-photon micros-copy to monitor arteriolar diameter and corresponding dynamic changes in intracellular Ca2+ of adjacent astrocytes, which are known to influence lumen diameter. OGD caused significant arteriolar constriction, starting at 10 min and reaching -15.8 ± 2.8% of baseline lumen diameter after 20 min (9 vessels). The cumulative constriction response, assessed as area under the time course lu-men diameter curve from 10-20 min, was 4.3-fold greater than control. 20-hydroxyeicosatetraenoic acid (20-HETE) is the ω-hydroxylation product of AA and is a potent physiological and pathophysiological inducer of smooth muscle contraction. OGD significantly increased cortical slice 20-HETE content from 18.93 ± 2.37 to 36.59 ± 4.67 (ng/mg protein) at the 20 min time point, suggesting it could be a mediator of constriction. Consistent with this, bath appli-cation of the ω-hydroxylase inhibitor, HET0016 (1 μM), reduced the 20 min OGD-induced reduction in lumen diam-eter from -15.8 ± 2.8% to -9.4 ± 2.5%. OGD increased perivascular astrocytic Ca2+ levels by 1.6-fold of baseline at 10 min, commensurate with reduced arteriolar lumen diameter and increased 20-HETE production. We can’t yet directly link astrocytic function with OGD-induced arteriolar constriction and AA. This will be an important component of ongoing experiments. Supported by the National Science and Engineering Research Council (Canada), Research Manitoba, and the Winni-peg Health Sciences Centre.


POSTER ABSTRACTSP-22 regulatIon of trpm2 channels by fyn kInase: ImplIcatIons for alzheImer’s dIsease

H. Gangadharappa*1, N. Lavine1, M. L. Johnston, J. C. Belrose, F. Caetano, J. F. MacDonald, and M. F. Jackson1 1Department of Pharmacology & Therapeutics, University of Manitoba; Neuroscience Research Program, Kleysen Institute for Advanced Medicine, Winnipeg Health Sciences Centre [email protected]

TRPM2 is a calcium-permeable non-selective cation channel gated by oxidative stress and implicated in neurodegen-erative diseases. Our recent work has shown that TRPM2 function is facilitated in response to amyloid-beta, more-over that genetic deletion of TRPM2 reduces pathological markers and cognitive decline in Alzheimer’s mouse model. Although TRPM2 channels are shown to be active and contribute to AD pathology, the mechanism promoting TRPM2 activation are not known. In light of past work suggesting that TRM2 function is regulated by tyrosine phosphorylation, herein we test whether Fyn kinase, known to be hyperactivated in AD, regulates TRPM2 function. To begin with, we investigated the potential role of Fyn kinase as a regulator of TRPM2 channel. Intracellular appli-cation of Fyn (1U/mL) potentiated TRPM2 currents in HEK293 cells expressing TRPM2 and in primary hippocampal neurons- an effect that was blocked by the Src family kinase inhibitor PP2 and more specifically by a Fyn inhibitory peptide. This inhibition was not reversed with an intracellular application of high concentrations of ADPR (10 mM), suggesting that phosphorylation does not alter agonist binding. Co-immunoprecipitation experiments in TRPM2-HEK cells confirmed a physical interaction of Fyn with TRPM2. Additionally, the amount of tyrosine phosphorylation of TRPM2 was related to the activation state of Fyn kinase. Future studies will determine whether recruitment of Fyn is a key determinant of increased TRPM2 function by amyloid-beta. Supported by the Canadian Institutes of Health Research and Research Manitoba.

P-23 contrIbutIon of pannexIn-1 actIvatIon to amyloId-beta Induced synaptotoxIcIty and neuro-toxIcIty

A. Yeung*, Y. Xie, N. Lavine, and M. F. Jackson Department of Pharmacology and Therapeutics, University of Manitoba; Neuroscience Research Program, Kleysen Institute for Advanced Medicine, Winnipeg Health Sciences [email protected]

Introduction: Calcium dysregulation induced by toxic soluble amyloid-beta oligomers (AβOs) is thought to lead to impairment of synaptic function (synaptotoxicity) and eventual cell death (neurotoxicity) in Alzheimer’s disease (AD). Processes which contribute to the loss of calcium homeostasis can therefore exacerbate the disease process. Pannexin 1 (Panx1) is a large-pore non-selective ion channel broadly enriched in the post-synaptic density of corti-cal and hippocampal neurons. The open state of Panx1 allows the flux of particles up to 1 kDA, including Ca2+, ATP, and IL-1β. Given its ability to mediate inward Ca2+ currents, we hypothesize that pathological activation of Panx1 contributes to calcium dysregulation in AD. Methods: Naturally secreted AβOs collected from the media of 7PA2 CHO cells expressing the variant of human APP mutation V717F was used as a proven treatment method. Acutely prepared hippocampal slices from Panx1 KO and WT mice were pre-treated with 7PA2 conditioned media (7PA2-CM) and CHO control media (CHO-CM). Changes in long-term potentiation (LTP) between groups was recorded by an established LTP protocol. Primary hippocampal neurons from Panx1 KO and WT mice were also chronically treated with 7PA2-CM. Cell death was assessed by LDH assay. Changes in neurite morphology and synaptic markers was assessed via MAP2, synaptophysin, PSD-95 and drebrin immunostaining and Western blot. Results: Panx1 WT slices treated with AβOs showed impairment in LTP, as seen by a significant decrease in fEPSP slope 60 minutes post-tetanus. However, Panx1 KO slices showed no significant change in LTP compared to control treatment. In primary hippocampal cultures treated with 7PA2-CM, dendritic degeneration and cell death were ob-served by 5 days as seen by a 3-fold increase in LDH release. There was a concomitant decrease in protein levels of the synaptic markers PSD-95 and drebrin. Conclusion: AβOs caused deficits in synaptic plasticity in acute hippocampal slices and induced synapse loss and cell death in primary cultured neurons. Preliminary data suggests that Panx1 contributes to the impairments in LTP. Sub-sequent experiments will evaluate whether cultured neurons from Panx1 KO mice are protected from AβO treatment. The mechanisms and consequences of Panx1 activation in response to AβOs will also be explored. Supported by the Canadian Institutes of Health Research.


POSTER ABSTRACTSP-24 InferrIng axon dIameters In the human corpus callosum

S.L. Herrera*1, M. E. Mercredi1, R. Buist2, K. M. Matsuda3, and M. J. Martin1,4 1Department of Physics & Astronomy, University of Manitoba; 2Department of Radiology, University of Manitoba; 3De-partment of Pathology & Pathophysiology, University of Manitoba; 4Department of Physics, University of Winnipeg [email protected]

Recent studies indicate possible changes in axon diameter distributions associated with neurological diseases such as autism, diabetes, dyslexia, and FASD, which underscores the significance of studying axon diameter. The methods currently available for measuring axon diameters are highly invasive, requiring sectioning of brain tissue for electron microscopy, and are limited due to fixation and cutting artifacts, the need to use post mortem tissue, and the use of only small tissue sample sizes. Here, we inferred the axon diameters in regions of interest within a human brain autopsy sample containing the corpus callosum, the ependymal layer, and the cortex. Images with 200 um in plane resolution were acquired using a 7T NMR system. Each of the 1260 images oscillating gradient spin echo images was acquired in 5.3 minutes with 2 averages, TR = 1250 ms, TE = 50 ms. Signals were fitted to a two compartment ActiveAx model using least squares minimization and mean axon diameters were extracted. The diameters of axons in the corpus callosum ranged from 1.03 ± 0.03 um to 1.44 ± 0.02 um. This is consistent with other histology mea-surements. As expected, no results were found in the cortex indicating parallel cylinders do not model the cells in the cortex very well. Our new method can infer cell diameters in the corpus callosum more accurately than previous methods and targets smaller axons which are more relevant for studies. Axon diameter inference will be confirmed with histological measurements in the same tissue. The next goal is to shorten the imaging time so that the method can be used clinically. Supported by NSERC, CFI, and Research Manitoba.

P-25 secreted amyloId precursor proteIn alpha prevents aberrant tau phosphorylatIon and un-folded proteIn response actIvatIon In the cortIces of dIabetIc mIce

B. Aulston*1,2, G. L. Odero2, and G. W. Glazner1,2 1Department of Pharmacology & Therapeutics, University of Manitoba; 2St. Boniface Hospital Albrechtsen Research Centre [email protected]

Hyperphosphorylation of the microtubule associated protein tau leading to tau aggregation and the formation of toxic neurofibrillary tangles is hypothesized to contribute to cognitive dysfunction and cell death in both Alzheimer’s disease (AD) and diabetic encephalopathy. Despite evidence that the APP cleavage product secreted amyloid pre-cursor protein alpha (sAPPα) activates insulin signaling pathways and can prevent tau phosphorylation in the brains of AD mice; the effects of sAPPα on diabetes-induced tau pathology remains unexplored. With this work, we studied the effects of sAPPα on the diabetic brain by rendering Tg, sAPPα-overexpressing mice STZ diabetic. No differences in fasting blood glucose or HbA1c levels were detected between diabetic Wt and Tg mice indicating that sAPPα-over-expression did not affect glucose utilization. However, overexpression of sAPPα blocked diabetes-induced tau phos-phorylation in cortical tissue after 16 weeks diabetes which was associated with decreased activation of the unfolded protein response (UPR). Furthermore, we found that sAPPα prevented diabetes-induced phosphorylation of AKT/GSK3. In total, these data show for the first time that sAPPα has a protective effect on diabetic brain tissue and war-rants further investigation into the therapeutic potential of sAPPα as a treatment for AD-associated insulin signaling impairment.


POSTER ABSTRACTS

P-26 the effect of levodopa dosage and duratIon on the progressIon of levodopa-Induced dyskI-nesIa In a rat model of parkInson’s dIsease

D. Zhang*1,4, A. Katako1,4, S. Li2,3, G. J. Kirouac2,3, and J. H. Ko1,4 1Department of Human Anatomy and Cell Science, University of Manitoba; 2Department of Oral Biology, University of Manitoba; 3Department of Psychiatry, University of Manitoba; 4Neuroscience Research Program, Kleysen Institute for Advanced Medicine, Winnipeg Health Sciences Centre [email protected]

Levodopa, the precursor molecule of dopamine, is a highly effective treatment for Parkinson’s disease (PD) patients. However, after a few years of treatment, half of all patients treated with the drug suffer from adverse side effects such as motor fluctuations and abnormal involuntary movements, known collectively as levodopa-induced dyskinesia (LID). The purpose of the present study was to create an animal model which closely resembles the human disease, and to evaluate the progression of LID in a rat model of PD. 6-hydroxydopamine (6-OHDA) was injected into the medial forebrain bundle (MFB) to induce a wide range of dopamine depletion in the nigrostriatal pathway. Two weeks after surgery, cylinder tests were performed to identify rats with Parkinsonism symptoms, which were then used for subsequent experiments. Five weeks later, rats with unilateral 6-OHDA lesions were given single daily intraperitoneal injections of levodopa (2, 4, 10 mg/kg)/benserazide (15 mg/kg) for 22 days. During the 3 weeks of treatment, limb, axial and orolingual abnormal involuntary movements (AIMs) were measured on days 1, 11 and 22. The 10 mg/kg dose induced dyskinetic symptoms starting on treatment day 1 and developed dyskinesia within a few days of treatment. The 4mg/kg dose induced dyskinetic symptoms on treatment day 4, and the 8 out of 11 rats developed dyskinesia. 4 mg/kg and 10 mg/kg doses reached their peak AIM scores before day 11. However, the 2 mg/kg dose showed dyskinetic symptoms after treatment day 11, and the AIM scores slowly increased until treatment day 22. By the end of the chronic treatment period, only half of the rats developed dyskinesia. Our results demonstrate that the 2 mg/kg dose of Levodopa over a 22 day treatment period in a rat lesion model of PD most closely approximates clinical progression of LID in PD. Supported by Research Manitoba, University of Manitoba, and NSERC.

P-27 the sonIc hedgehog sIgnalIng pathWay In development of cerebellar granule cells

X. Jiao*, N. Ashtari, M. Rahimi-Balaei, and H. Marzban Department of Human Anatomy and Cell Science, University of Manitoba; The Children’s Hospital Research Institute of Manitoba (CHRIM) [email protected]

During development, cerebellar granule cell precursors arise from the rhombic lip and form the external germinal zone. The granule cell precursors proliferate and then migrate to the granule cell layer and differentiate into mature granule cells. In this process, the sonic hedgehog (Shh) and N-myc pathways are important promoters for granule cell precursor proliferation. The lysosomal acid phosphatase 2 (Acp2) mutant mouse (naked-ataxia, nax) shows a significant reduction in granule cells in the cerebellum. We hypothesize that the decrease N-myc expression inter-rupts the Shh pathway in cerebellar granule cells neurodevelopmental disorders. We used nax mice and wild-type siblings as controls in this study. In vivo and in vitro immunohistochemistry and Western-blotting were used to detect molecular expression. In the nax mouse, there is an 80% reduction in granular cells in nax mice cerebellar cortex compared with wild-type sibling mice during postnatal development. The Shh expression changed with a delay in the nax cerebellum compared with wild-type. Our data showed strikingly reduced N-Myc expression in the nax cerebellum, which was accompanied by an increase in proteasome activity. This study suggests that Shh and the N-myc pathway are impaired in the nax mouse and granule cells proliferation is inhibited during cerebellar develop-ment. The significant reduction in proliferation and probably differentiation of granule cells in the nax mouse reveals that Acp2 mutation affects proteasome activity and dysregulates N-myc expression in the Shh pathway. Supported by the Canadian Institutes of Health Research.


POSTER ABSTRACTSP-28 toWard a clInIcal measurement of axon dIameters In the human corpus callosum

M. E. Mercredi*1, S. L. Herrera1, R. Buist2, K. M. Matsuda3,4, and M. J. Martin1,5 1Department of Physics & Astronomy, University of Manitoba; 2Department of Radiology, University of Manitoba; 3De-partment of Pathology & Pathophysiology, University of Manitoba; 4Department of Physics, University of Winnipeg [email protected]

The measurement of brain axon diameter distributions is important in neuroscience. Recent studies indicate possible changes in distribution of axon diameter, in a variety of neurological disorders such as Alzheimer’s, autism, diabe-tes, dyslexia, fetal alcohol spectrum disorders and schizophrenia which underscore significance of studying axon diameter distribution. Our new non-invasive method of axon diameter measurements uses high gradient strengths and long imaging times. Here as a first step to making our method clinically relevant we studied the accuracy of measurements using fewer images to determine if we could shorten imaging time. A portion of normal-appearing corpus callosum from an autopsy human brain was obtained, which did not demonstrate any pathological changes. This sample was fixed and placed in agarose within a 15 mL sample tube. Images were acquired using a 7T Bruker Avance III NMR system with a BGA6 gradient insert. Images were collected using 15 oscillating gradient (OG) fre-quencies ranging from 50 Hz to 750 Hz and five gradient strengths for each frequency. Signals were fitted to a two compartment ActiveAx model using least squares minimization to extract mean axon diameter. Higher OG frequen-cies were then removed and the remaining data were refitted to the model to see how fitted parameters changed to determine if certain images could be excluded from data collection in clinical settings. We found that reducing the number of OG frequency measurements can shorten imaging time by a factor of approximately 2 which results in a decrease in precision of 8% to 32%. More studies are needed to shorten the imaging time further by reducing the number of gradients and averages in order to create a clinically applicable sequence. Supported by NSERC, CFI, and Research Manitoba.

P-29 mechanIsm of pannexIn channel actIvatIon In alzheImer’s dIsease

C. Patil*, N. Lavine, and M. F. Jackson Department of Pharmacology & Therapeutics, University of Manitoba [email protected]

Loss of Ca2+ homeostasis, whereby increased cytosolic Ca2+ concentration leads to neurotoxicity, is one of the leading hypotheses underlying the pathology of Alzheimer’s disease (AD). In this regard, amyloid-β oligomers (AβOs) have been suggested to provoke aberrant activation of Ca2+ permeable NMDA receptor (NMDARs). Previous studies from Jackson lab has shown that, overactivation of NMDARs provokes pannexin channel activation, however the signaling cascade is yet to be elucidated. The main objective of this study is to establish the mechanism through which AβOs facilitate pannexin activation downstream of NMDAR stimulation. Hippocampal enriched neuronal cul-tures from CD1 mice were used for electrophysiological recordings. The application of NMDA for duration of 5 min reliably evoked pannexin currents which were blocked by Lanthanum. To confirm the role of NMDAR in generating pannexin currents, AP-5 (NMDAR antagonist) was used. Blocking NMDAR inhibited generation of pannexin currents. Next, to investigate the specific NMDAR subunit responsible for pannexin activation, the role of NR2A (neuropro-tective) & NR2B (neurodegenerative) was determined. To do so, I used NMDAR subunit specific blockers TCN-201 (NR2A) & Ro-25-6981 (NR2B). Interestingly I discovered, blocking NR2A inhibited pannexin currents & blocking NR2B had no effect. The role of ryanodine receptors (RyRs), activated downstream of NMDAR and shown previous-ly by the Jackson lab to contribute to pannexin channel activation, was confirmed using a novel channel stabiliz-er (S107) as it inhibited the generation of pannexin currents in response to NMDA. The current study establishes the downstream activation of pannexin channel in a NR2A & RyR dependent manner. Ongoing work will determine whether AβOs sensitizes pannexin via the pathway described. Investigating the signaling cascade for pannexin acti-vation may influence discovery of potential therapeutic targets for impeding detrimental effects of AβOs.


POSTER ABSTRACTSP-30 role of trpm2 In mIcroglIal actIvatIon outcome

P. Raghunatha*, L. Tessler, M. Stevenson, M. F. Jackson and T. M. Kauppinen Department of Pharmacology & Therapeutics, University of Manitoba; Neuroscience Research Program, Kleysen In-stitute for Advanced Medicine, Winnipeg Health Sciences Centre [email protected]

Microglia, the immune cells of the brain are drivers of neuroinflammation and thus can promote neuronal death. Microglial activation results in a pro-inflammatory phenotype (M1) from which microglia returns to their resting state (M0) via immune resolution (M2) phenotype. In Alzheimer’s Disease microglia remain in M1, which our lab has shown to be driven by nuclear enzyme poly(ADP-ribose) polymerase-1 (PARP-1). My goal is to understand the mechanism that promotes continuous microglial PARP-1 activation maintaining them in M1 phenotype. The Ca2+ permeable non-selective cation channel, transient receptor potential melastatin-2 (TRPM2) depend on ADPRs, a product of PARP-1 activation. Notably calcium is required for PARP-1 activation. The hypothesis tested in the present study is that TRPM2 promotes constitutive PARP-1 activation via increasing Ca2+ influx and thus causes prolonged microglial pro-inflammatory activation phenotype. Studies were performed in primary cultures of cortical murine mi-croglia. TRPM2 currents were evoked by ADPR exogenously supplied via the patch pipet during whole cell recordings, which demonstrates the functional presence of TRPM2 in microglia. Interestingly, TRPM2 current in microglia pre-pared from male mice were 3-fold larger than in female. In the absence of exogenously supplied ADPR, excitotoxic glutamate stimulation (25 µM for 24 hrs) also induced TRPM2 currents, presumably reflecting endogenous ADPR production by PARP-1. TRPM2 currents induced by glutamate were larger in female than in male microglia (128 vs. 51%). Glutamate receptor agonist, NMDA induced significant nitric oxide release in microglia cultures prepared from WT mice, but not in TRPM2 KO mice. This ongoing work demonstrates the importance of TRPM2 channels in main-taining microglial pro-inflammatory responses upon glutamate excitotoxicity and suggests potential sex differences in regulation.

P-31 a novel quantItatIve method of predIctIng levodopa Induced dyskInesIa In parkInson’s dIs-ease

M. Aljuaid*, D. E. Hobson, A. Borys, K. Williams, A. Katako, T. Chung, L. Ryner, A. L. Goertzen, and J. H. Ko Department of Human Anatomy & Cell Science, University of Manitoba [email protected]

The forefront treatment of Parkinson’s disease (PD) is Levodopa. Previously, it has been reported that cerebral blood flow is increased while cerebral metabolic rate is decreased in key subcortical regions including the putamen when patients are treated with Levodopa. This may be associated with Levodopa-induced dyskinesia (LID). Objectives: We investigate if clinically determined anti-parkinsonian medications also dissociates the CBF and glu-cose metabolic activity using perfusion MRI (pMRI) and FDG-PET, respectively. We further propose a novel method to quantify the degree of dissociation in the putamen which may have potential to be used as a biomarker for LID. Methods: Ten PD patients (5 with LID and 5 without LID) were scanned with FDG-PET (a probe for glucose metabo-lism) and perfusion MRI (pMRI; a probe for cerebral blood flow (CBF)) both when they are ON and OFF medications. We further proposed a novel analytical method to quantify the degree of dissociation in the putamen using only the ON condition scans, Putamen-to-thalamus Hyper-perfusion/hypo-metabolism Index (PHI). Results: A significant interaction effect has been found in the putamen (p=0.023). Post-hoc analysis revealed that anti-parkinsonian medication consistently normalized the pathologically hyper-metabolic state of the putamen which was not followed by uniform increase in CBF. This dissociation was especially predominant in patients with LID com-pared to the ones without. PHI correctly classified 8 out 10 patients in this study. Conclusions: PHI may have a potential to be used as a biomarker to identify patients who are at-risk of developing LID and who will most likely benefit from anti-angiogenic treatment. Supported by Manitoba Medical Service Foundation, Natural Sciences and Engineering Research Council of Canada, Brain Canada, University of Manitoba, King Saud University, Riyadh, Saudi Arabia, and Saudi Arabian Culture Bureau in Canada.


POSTER ABSTRACTS

P-32 the role of a novel subset of mesencephalIc neural crest derIved cells In cerebellar nucleI development In mIce

M. Rahimi-Balaei*, N. Ashtari, X. Jiao, and H. Marzban Department of Human Anatomy and Cell Science; The Children’s Hospital Research Institute of Manitoba (CHRIM); [email protected]

During cerebellar development, cerebellar nuclei (CN) neurons and Purkinje cells are the earliest born among the different neuronal subtypes. Purkinje cells are the sole output of the cerebellar cortex that project to the CN. The CN represents the main output of the cerebellum, which is generated from the rhombic lip. In this study, we investigat-ed new origin for part of the CN neurons during early cerebellar development. We used whole mount/section immu-nohistochemistry, cerebellar culture, Western blot, and embryonic cultures to examine the origin of a new subset of CN neurons from the mesencephalon during early cerebellar development. Our results show that a subset of CN neurons, which are immunopositive for α-synuclein (SNCA) and orthodenticle homeobox 2 (Otx2, mesencephalic marker), originate from the mesencephalon and cross the isthmus toward the rostral end of the nuclear transitory zone. Interestingly, double immunostaining of the SNCA with Otx2 or p75 neurotrophin receptor (p75ntr) suggests that these cells are probably derived from neural crest cells. We also showed that this population of neurons with nerve fibers terminates at the subpial surface of putative lobules VI/VII. The SNCA+/Otx2+/p75+ cells, which divide the cerebellar primordium into rosterodorsal and caudoventral compartments, show increased cleaved caspase-3 (CC3+) activation. These results suggest that early CN neurons originate from the mesencephalic neural crest pop-ulation; contrary to popular opinion that Otx2 has been shown to be involved in prosencephalon and mesencepha-lon establishment, but not the rhombencephlon. The p75 immunopositive cells which show activation of caspase-3 during embryonic stage suggest their role in proliferation, differentiation, survival and axonal guidance. The pres-ence of migratory mesencephalic derived neural crest cells in the nuclear transitory zone suggests that these neu-rons/fibers have a regulatory role as a signaling center that may play as an intrinsic organizer during early cerebellar development.

P-33 elucIdatIng the role of bone morphogenetIc proteIn 4 In endogenous cell response and as-trocyte reactIvIty folloWIng spInal cord Injury

C. G. Hart*, S. M. Dyck, H. Kataria, K. T. Santhosh, S. Karimi-Abdolrezaee Department of Physiology & Pathophysiology, University of Manitoba [email protected]

Reactive astrocytes modulate the spinal cord injury (SCI) microenvironment by producing a plethora of inhibitory factors. In this study, we demonstrate that activated astrocytes influence the properties of neural stem/progenitor cells (NPCs) by upregulating bone morphogenetic protein 4 (BMP4). BMP4 is an essential morphogen in the develop-ing CNS with an established role in modulating astrocyte differentiation. Our clinically-relevant model of compressive SCI in rats showed that BMP4 is robustly upregulated in the acute phase of SCI between 1 and 3 days post injury. To date, the role of BMP4 in acute SCI has remained largely unknown. Our objective is to understand the role of BMP4 in acute injury mechanisms and while aiding in developing repair strategies for CNS injuries. To investigate the im-pact of BMP4, we delivered an endogenous inhibitor of BMP ligands, noggin, into our SCI rat model via mini-osmotic pumps at the time of injury. We performed tissue analysis at 1, 3 and 7-day time-points following SCI and noggin treatment. We used in vitro primary cultures including rodent NPCs and astrocyte-microglia to assess the direct effects of BMP4. Assessments were conducted by immunocytochemistry, Greiss assay, slot blot, and Western blot. BMP4 protein expression was significantly and transiently upregulated following compressive SCI in rats at 1 and 3 days post injury (dpi). Reactive astrocytes showed to be a significant source of BMP4 in vitro. NPCs and astrocyte cultures responded to BMP4 by Smad1/5/8 phosphorylation, the canonical pathway for BMP signaling. NPCs treated with BMP4 (30-100ng/ml) decreased their proliferation, and increased their viability while predominantly differen-tiating into astrocytes. These effects were inhibited when BMP4 was co-treated with noggin. In cultures of reactive astrocytes, BMP4 had no significant effect on GFAP expression, but increased CSPG production. Our findings indicate that BMP4 is upregulated following SCI and promotes astrogliosis in mature astrocytes. BMP4 also promotes the differentiation of activated NPCs into astrocytes that contribute to scar formation. Our data has identified a new role for BMP4 in pathophysiology of SCI that requires further elucidation. Supported by Natural Sciences and Engineering Research Council of Canada and Craig H. Neilsen Foundation.


POSTER ABSTRACTS

P-34 selectIve expressIon of desIgner receptors exclusIvely actIvated by desIgner drugs (dre-adds) In thoraco-lumbar cholInergIc Interneurons In genetIcally modIfIed mIce

X. Chen*, P. Bhullar, K. Armstrong, M. Nazzal, and K. Stecina Department of Pathology & Pathophysiology, University of Manitoba; Spinal Cord Research Centre, Rady Faculty of Health Sciences, University of Manitoba [email protected]

Introduction: Respiration, locomotion and blood pressure regulation are controlled in part by spinal cholinergic interneurons. After spinal cord injury, when the regulation of spinal cholinergic neurons is impaired, their aberrant activity contributes to autonomic dysreflexia. If selective control over the activity level of the cholinergic spinal inter-neurons could be achieved, it may reduce the severity or the frequency of autonomic dysreflexia. DREADDs provide novel means for modifying activity in selective neural pools. Objective: We aimed to target sub-populations of cholinergic thoraco-lumbar neurons by commercially available DREADDs in a genetically modified mouse line carrying Cre-recombinase in cholinergic neurons for establishing whether selective activation of spinal cells is feasible in adult mice. Methods: The spinal injection of DREADDs that consists of mutated, human muscarinic G-protein coupled receptors conjugated with adeno-associated viral vectors with a double-floxed inverse open-reading frame – pAAV-hSyn-DIO-hM3D(Gq) were used. Following a minor laminectomy, injections into low thoracic or lumbar segments were done by a device from Neurostar Gmbh., DE developed originally for brain stereotaxic work. After recovery (7 to 126 days) mice were transcardially perfused and cords were harvested for immunohistochemical and fluorescent microscopic analysis. Results: Injections of 80 to 250 nL volumes at single sites were found to provide transfection of 100-250 neurons in the thoracic and the lumbar spinal cords. Selective transfection of cholinergic interneurons vs. motoneurons was possible by controlling the depth at which the injections were performed. Expression of constructs in non-cholinergic neurons was low. Conclusions: The use of these constructs is a viable method for cholinergic cell transfection in the spinal cord. By this approach, the contribution spinal cholinergic neurons to various physiological functions in the healthy or the injured spinal cord, including autonomic dysreflexia conditions could be determined. Supporting Funds: The Dr. Paul H.T. Thorlakson Foundation Fund, the University of Manitoba, NSERC (K.S.), and Research Manitoba (studentship to P.K.B.).

P-35 pathogenesIs of chIldhood ataxIa WIth central nervous system hypomyelInatIon

G. Nagra*, X. Mao, and M. R. Del Bigio Children’s Hospital Research Institute of Manitoba; Department of Pathology & Pathophysiology, University of Mani-toba [email protected]

Childhood ataxia with central nervous system hypomyelination (CACH) is rare autosomal recessive disorder char-acterized by destruction of the cerebral white matter, typically beginning in infancy or childhood. It is caused by mutations in one of the five genes (EIF2B1-5) that generate the eukaryotic translation initiation factor 2B complex, which subserves GDP to GTP conversion and allows delivery of tRNA to initiate protein translation. The eIF2B protein complex has not been studied in human brain. A cell culture study (Kar et al., 2013) showed the mRNA that encodes eIF2B2 is translated locally in the axons of rat sympathetic neurons. We performed Western blot analysis on (N=5) normal autopsy brain samples of gestational age 19, 25, and 40 weeks and 9 and 60 years using one eIF2B2 and three different eIF2B5 antibodies. Two antibodies to eIFB2 showed slightly greater expression of the protein in the developmental period. Immunostaining showed localization of eIF2B2 in axons of cerebral white matter beginning at 18 weeks gestation; by term birth and in adulthood the expression was more generalized including cell bodies in the cerebral cortex. The brain of a 7 month female with genetically proven CACH was compared to age-matched control. The cerebral white matter contained only sparse myelinated axons, macrophages (CD68 immunoreactive), frag-mented axons (neurofilament immunoreactive), reactive astrocytes (alpha B crystallin immunoreactive), and rare ubiquitinated structures. Electron microscopy showed loss of cerebral axons, macrophages with myelin debris, and rare empty myelin sheaths. Early localization of eIF2B in normal cerebral axons in the white matter and the appear-ance of empty myelin sheaths in CACH suggests that CACH might be a primary axonal degenerative disease rather than a glial dysfunction disease. Supported by Canada Research Chairs program.


POSTER ABSTRACTS

P-36 neuregulIn-1 posItIvely modulates glIal response and Improves neurologIcal recovery fol-loWIng traumatIc spInal cord Injury

A. Alizadeh*, S. M. Dyck, H. Kataria, D. Nguyen, K. T. Santhosh, and S. Karimi-Abdolrezaee Department of Pathology & Pathophysiology, University of Manitoba [email protected]

Introduction: Astrogliosis and neuroinflammation play pivotal roles in the secondary injury mechanisms after spinal cord injury (SCI) with both pro- and anti-regenerative effects. We previously reported for the first time that expres-sion of Neuregulin-1 (Nrg-1) is dramatically and permanently downregulated in acute SCI. Glial and immune cells express Nrg-1 receptors, ErbB2, 3, 4, suggesting the potential ramifications of Nrg-1 dysregulation on glial activity and neuroinflammation. In this study, we sought to unravel the role of Nrg-1 in regulating astrogliosis and immune response following SCI. We demonstrate that Nrg-1 exerts anti-inflammatory and neuroprotective effects that can be culminated in improved recovery of function following SCI. Methods: In vitro, we used primary mixed culture of rat astrocytes and microglia activated by lipopolysaccharide (LPS). In vivo, we employed a rat model of compressive SCI. We delivered recombinant human Neuregulin-1 (rhN-rg-1β1) intrathecally for up to 6 weeks. We conducted Western blotting, immunoprecipitation, gelatin zymography and stereology-based immunohistology at 1, 3, 7, 14 and 70 days post-SCI. SCI rats were assessed for their loco-motion and sensory recovery weekly. Results: We show that Nrg-1 treatment attenuates several characteristics of activated glia such as reduction in chon-droitin sulfate proteoglycans (CSPGs), nitric oxide (NO), interleukin (IL)-1β and tumor necrosis factor (TNF)-α. In SCI, Nrg-1 promotes an anti-inflammatory immune response associated with increased IL-10 and arginase-1 expres-sion and a global decrease in pro-degenerative markers such as IL-1β, TNF-α and matrix metalloproteinases (MMP-2 and 9) after SCI. Nrg-1 also reduces astrocytic glial scarring by decreasing GFAP and CSPGs expression in the SCI lesion. Mechanistically, we demonstrate that Nrg-1 effects on activated glia are mediated through ErbB2/3 heterod-imer complex. Intracellualrly, Nrg-1 exerts its effects through downregulation of Myd88, a downstream adaptor of Toll-like receptors, and phosphorylation of Erk1/2 and STAT3. Importantly, Nrg-1 treatment significantly improves functional recovery following SCI. Conclusion: Our findings for the first time provide novel insight into the promising role of Nrg-1 in modulating acti-vated glial and immune cells in repair and recovery following SCI. Supported by the CIHR, CPA, and RM.

P-37 regulatIon of a synaptIc pathWay In autIsm spectrum dIsorders

R. T. Roppongi*, S. Dhume, K. Champagne-Jorgensen, Y. Wang, T. J. Siddiqui Department of Physiology and Pathophysiology, University of Manitoba; Neuroscience Research Program, Health Science Centre Winnipeg [email protected]

Neurexin-LRRTM is a key synapse organizing complex, which controls the molecular composition and functional properties of excitatory synapses. Both neurexins and LRRTMs are implicated in cognitive disorders such as au-tism spectrum disorders (ASD) and schizophrenia. Lack of LRRTM4 in mice reduces excitatory synapse number and function by up to 35% across brain regions and compromises several forms of synaptic plasticity. Here, we investi-gated the functional significance of neurexin interaction with LRRTMs. Primary hippocampal neurons were cultured from embryonic day 18 rat embryos. All neurexins were knocked down in primary neurons using shRNAs delivered by AAV. For rescue experiments, hippocampal neurons were transfected at day in vitro (DIV) 0 using nucleofection (AMAXA Biosystems, Lonza) with different deletion mutants of neurexins. Neurons were co-cultured with transfect-ed COS-7 cells at DIV14-15 to assess synaptic induction. Co-cultures were subsequently fixed at DIV15, stained for presynaptic and postsynaptic markers and imaged using fluorescence microscopy. We identified the motifs of neurexin and LRRTMs required for their interaction. We also identified the minimal domain of neurexin required to execute its functions. Our studies reveal a novel mode of interaction between neurexins and LRRTMs essential for the development of excitatory synapses. Supported by the Canadian Institutes of Health Research. Supported by the Canadian Institutes of Health Research.


POSTER ABSTRACTSP-38 dovItInIb enhances temozolomIde effIcacy In glIoblastoma

T. Thanasupawat*, S. Natarajan, A. Rommel, A. Glogowska, H. Bergen, J. Krcek, M. Pitz, J. Beiko, I. M. Verma, S. Ghavami, T. Klonisch, and S. Hombach-Klonisch Department of Human Anatomy and Cell Science, University of Manitoba [email protected]

Glioblastoma (GB) is a highly aggressive form of primary brain tumor which is usually fatal. Temozolomide (TMZ) is an alkylating agent commonly used in treatment of GB. TMZ-induced DNA damage is repaired by O6-methyl-guanine-DNA methyltransferase (MGMT) and the base excision repair (BER) process. The non-histone chromatin protein High Mobility Group AT-hook protein 2 (HMGA2) binds to the DNA minor groove and its BER enzyme activity increases TMZ chemoresistance. We showed that HMGA2 antagonizes TMZ-induced DNA damage and knockdown of HMGA2 caused enhanced apoptosis in GB cells exposed to TMZ. We hypothesized that minor groove binding drugs can compete with HMGA2 for DNA binding and attenuate HMGA2 protective functions in GB. Dovitinib (DOV) is a FDA-approved broad kinase inhibitor and DNA minor groove binder drug. DOV crosses the blood brain barrier and is currently in clinical trials for treatment of GB patients. We found that DOV enhanced TMZ sensitivity by downregu-lating HMGA2, key factors of BER, and MGMT in GB. DOV also inhibited the phospho-STAT3Tyr705-LIN28A pathway which serve as an upstream regulator of HMGA2. Combination treatment of TMZ and DOV enhanced TMZ sensitivi-ty by increasing DNA damage and apoptosis. Sequential treatment with DOV and TMZ markedly decreased the cell viability of patient GB cells. Our results identified a new and attractive therapeutic approach of DOV sensitization for improved TMZ response in GB patients.

P-39 role of cx36 proteIns In perIpheral nerves durIng the trIple response and paIn

P. K. Bhullar*, B. Lynn, J. I. Nagy, and K. Stecina Department of Physiology & Pathophysiology, University of Manitoba [email protected]

Introduction: Gap junctions allow direct cell-cell communication and form electrical synapses between neurons primarily via the gap junction protein connexin36 (Cx36). We examined the potential contribution of Cx36 in spinal dorsal root ganglia and peripheral nerves to the classic triple response(flare, wheal, edema) in pain and inflamma-tion mediated by release of neuromodulators from peripheral sensory nerve endings (e.g., nociceptors). The flare reflects increased blood flow beyond the injured area and the wheal is due to changes in the vascular permeability. Studies conducted in the 1980s suggested that electrical coupling between unmyelinated C-fibers in the periphery may contribute to these responses. Objectives: We aimed to obtain evidence for Cx36 expression in primary sensory neurons, and to quantify the con-tribution of Cx36-containing gap junctions to plasma extravasation responses following stimulation of nociceptors. Methods: Immunofluorescence for EGFP as a reporter for Cx36 expression was examined in relation to substance P and CGRP localization in dorsal root ganglia (DRG) and peripheral sensory fibers. In addition, wild-type (WT) and Cx36 knockout (KO) mice were used for application of noxious stimuli (xylene, formalin, electrical stimulation of the sciatic nerve). Extravasation of Evans Blue dye from the circulation in the limbs was monitored via spectrophotome-try, laser Doppler flux and in vivo fluorescence imaging after noxious stimulation in anesthetized mice. Results: In DRG, EGFP was co-localized with SP and CGRP in small type B neurons. Greater peak responses as well as a faster rate of change in Evans Blue extravasation was found in WT vs. Cx36 KO mice. Conclusions: The evidence for Cx36 expression in neurons giving rise to unmyelinated C-fibers and the enhanced early vascular response after nociceptor are consistent with earlier reports of direct electrical coupling between C-fi-bers and with suggestions that such coupling contributes to the axon reflex. Supported by NSERC (J.I.N. & K.S.) and Research Manitoba (studentship to P.K.B.).


POSTER ABSTRACTSP-40 lrrtm1 and lrrtm2 regulate cIrcuIt specIfIc synapse development and behavIour

S. Dhume*, and T. J. Siddiqui Department of Pathology & Pathophysiology, University of Manitoba; Neuroscience Research Program, Kleysen Insti-tute for Advanced Medicine, Winnipeg Health Sciences Centre [email protected]

Leucine rich repeat transmembrane neuronal proteins (LRRTM) are postsynaptic cell adhesion molecules that pro-mote excitatory synapse development through binding to their presynaptic receptors, neurexins. LRRTM1 and 2 are expressed at high levels in distinct areas of the brain and are implicated in autism, schizophrenia and other neuropsychiatric disorders. Preliminary data from our lab show that embryonic-stage deletion of LRRTM1 and 2 in the hippocampus of 6 weeks old mice leads to large deficits in excitatory synapse numbers, synaptic transmission & contextual fear memory. The current study explores the role of LRRTM1 and 2 in the formation and maintenance of synapses and how they regulate behaviour. We assessed their joint role in synapse development using LRRTM1, LRRTM2 and LRRTM1/2 conditional double KO (cKO) mice. We focused on dorsal CA1 region of hippocampus because of its role in learning and memory. In preliminary studies, AAV5-eYFP-CamKII (control) or AAV9.CamKII.HI.eG-FP-Cre (test) were stereotaxically delivered to the dorsal CA1 of LRRTM2 double-floxed mice. Behavioural tests were conducted to assess the working and spatial memory of test and control mice. Further, quantitative real-time PCR, western blot analysis and fluorescence microscopy was done to confirm knockout of LRRTM2 in dorsal CA1. Deficits in spatial and working memory were observed in the test but not the control mice. This study will contribute to the evidence that synapse organizing proteins control synapse development and cognition. Supported by NSERC.

P-41 collateralIzatIon of projectIons from the paraventrIcular nucleus of the thalamus to the nucleus accumbens, bed nucleus of the strIa termInalIs, and central nucleus of the amygdala

X. Dong*, S. Li, and G. J. Kirouac* Department of Oral Biology, University of Manitoba [email protected]”

The paraventricular nucleus of the thalamus (PVT) is a midline thalamic nucleus with dense projections to the nucle-us accumbens (NAc), dorsolateral region of the bed nucleus of the stria terminalis (BSTDL) and the lateral/capsular region of the central nucleus of the amygdala (CeL/CeC). Recent experimental evidence indicates that the PVT is involved in both appetitive and aversive behaviors. However, it is unknown if subgroups of neurons in the PVT inner-vate different subcortical targets or if the same neurons issue collaterals to multiple areas. To address this issue, we injected two different fluorescent retrograde tracers, cholera toxin subunit B conjugated to Alexa Fluor-488 or Alexa Fluor-594, into different pairs of the subcortical targets including different parts of the NAc (shell, core, dorsome-dial shell and ventromedial shell), BSTDL and amygdala (basolateral amygdala and CeL/CeC). Our result indicates a moderate to high level of collateralization of projections from neurons in the PVT to NAc, BSTDL and CeL/CeC suggesting a potential importance of the PVT in simultaneously coordinating the activity of key regions of the brain involved in mediating emotional and motivational behaviors. We also observed a difference in the subcortical targets innervated by the anterior PVT (aPVT) and posterior PVT (pPVT) showing that more neurons in the aPVT innervate the dorsal medial part of the NAc shell while more neurons in the pPVT innervate the ventral medial NAc shell, BST-DL and CeL/CeC. This observation is suggestive of a potential functional difference between the aPVT and pPVT. Supported by the Canadian Institutes of Health Research (CIHR).


POSTER ABSTRACTS

P-42 optImIzed t2-WeIghtIng for gradIent and spIn echo (grase) based t1W/t2W mrI ratIo mappIng In human braIn

M. N. Uddin1, S. M. Courtney2, and C. R. Figley1 1Department of Radiology, University of Manitoba; 2Department of Psychological and Brain Sciences, Johns Hopkins University [email protected]

The ratio of T1-weighted (T1w) and T2-weighted (T2w) MRI images (T1w/T2w) has become an increasingly pop-ular technique for quantifying brain tissue changes associated with neurodevelopment, aging, and a variety of neurodegenerative disorders. However, although it is self-evident that T1w/T2w ratios increase with the amount of T2-weighting in the T2w image – which is determined by the echo time (TE), all else being equal – longer TEs also reduce the signal-to-noise ratio (SNR) of the T2w image, and it is not clear how these SNR characteristics affect the stability/reliability of T1w/T2w measurements. Therefore, the purpose of this work was to investigate how differ-ent amounts of T2-weighting affected T1w/T2w measurements in order to determine whether there is an optimal amount of T2-weighting. The T1w anatomical images were acquired using a conventional 3D magnetization pre-pared rapid acquisition gradient echo (MPRAGE) sequence, and a series of T2-weighted images were extracted from a multi-echo 3D gradient and spin echo (GRASE) sequence. All the images were acquired at 3T MRI from 10 neu-rologically healthy human brains. Myelin water fraction (MWF) maps were calculated from the GRASE data. Image analyses were performed using MATLAB, SPM12, MRIStudio and SPSS. After high-dimensional non-linear warping and signal intensity normalization, region-of-interest (ROI) analyses were performed on T1w/T2w ratios and MWF maps in 12 bilateral brain structures from the JHU_MNI_SS (“Eve”) atlas. Our findings indicate that T1w/T2w ratios based on T2w images with TE ≈ 120-160 ms yielded the highest degree of reproducibility across subjects and brain regions, and that TE ≤ 160 ms yielded modest, but significant correlations with MWF measurements. As a result, we recommend that future studies using T1w/T2w ratios should: 1) acquire T2w images with TE ≈ 120-160 ms at 3T, and 2) use the T1w/T2w measurements as general measures of tissue microstructure. Supported by NSERC and Brain Canada.

P-43 endothelIal nmda receptors are Involved In astrocyte-medIated cortIcal vasodIlatIon

A. Hogan-Cann*, L. Lu, A. Globa, S. Bamji, J. I. Nagy and C. M. Anderson Department of Pharmacology & Therapeutics, University of Manitoba; Neuroscience Research Program, Kleysen In-stitute for Advanced Medicine, Winnipeg Health Sciences Centre [email protected]

Glutamatergic neurotransmission results in a local hyperemic response that is mediated by neuronal NMDA receptors and nitric oxide (NO), or by inducing release of vasodilatory gliotransmitters from perisynaptic astrocytes. Howev-er, neither of these mechanisms is endothelium-dependent, leaving neuro-endothelial coupling as a key conceptual deficit in understanding FH. The current study was designed to test the possibility that NMDA receptors are ex-pressed by brain endothelial cells and participate in neurovascular coupling. Experiments in primary mouse brain microvascular endothelial cultures revealed expression of the pan-NMDA receptor subunit, GluN1, and NO produc-tion in response to NMDA receptor co-agonists, glutamate and D-serine, in a manner sensitive to NMDA receptor antagonists, channel activity, chelation of intracellular Ca2+ and eNOS inhibition. GluN1 immunoreactivity was also detected in brain endothelium in situ, with preferential localization to brain-facing endothelial membranes. Two-pho-ton (TP) flash photolysis of NP-EGTA in astrocytes adjacent to cortical slice arterioles both produced increases in endothelial NO production and lumen diameter. These effects were significantly mitigated by competitive antago-nists of NMDA receptor glutamate or co-agonist binding sites, and by eNOS loss of function. To distinguish between neuronal and endothelial NMDA receptors, we created conditional endothelial NMDA receptor loss of function mice by crossing “floxed” Grin1 animals with a Tie-2 Cre recombinase driver line. This strategy resulted in greater than 50% loss of endothelial GluN1 (eGluN1) expression in cultures and commensurate reduction in NO production. In acute cortical slices, conditional eGluN1 loss of function significantly mitigated endothelial NO generation and vasodilatory responses in situ, produced by stimuli including TP astrocytic Ca2+ uncaging and direct vascular application of NMDA receptor agonists. Endothelial-selective GluN1 silencing was associated with altered metabolism of arachidonic acid, favouring enhanced tissue levels of the smooth muscle constrictor, 20-HETE, relative to the vasodilatory metabo-lite, PGE2. Our results identify a novel mechanism of neuro-endothelial coupling by showing that endothelial NMDA receptors mediate activity-dependent, glutamatergic neurovascular signaling.


POSTER ABSTRACTS

P-44 development of a reporter system alloWIng real-tIme monItorIng of neurodegeneratIon In prIon dIsease

M. J. Martin*1, and S. A. Booth1,2 1Department of Medical Microbiology and Infectious Diseases, University of Manitoba; 2National Microbiology Labora-tory, Public Health Agency of Canada [email protected]

Prion diseases are a relatively unknown neurodegenerative disease caused by an infectious prion protein. Current methods of studying the neurodegeneration caused by the disease require sacrificing subjects at specific time-points to allow for further analysis. In vivo optical imaging is a promising method which allows the real-time monitoring of gene expression in cells in vitro or in vivo. The objective of my research is to develop a reporter system that can be used to observe the expression of genes which are known to be induced in degenerating neurons, allowing real-time monitoring of neurodegeneration in prion disease. Regulatory regions of genes which have previously been shown to be induced during the early stages of prion disease will be assembled onto an Adeno-Associated Virus (AAV) vec-tor, upstream of a reporter gene. AAVs will be used to deliver the reporter constructs into mouse primary neuron cultures, which will then be exposed to infectious prion proteins. Successful reporter constructs will be identified to be adapted for use in vivo. Current work has demonstrated a high neuron specificity of the selected AAV serotype. Additionally, this AAV serotype has been used to deliver control reporter constructs into mouse primary neurons. This work demonstrates that the use of a neurotropic AAV serotype will allow delivery of a reporter construct into neurons. This reporter construct will allow monitoring of expression of genes known to be induced in neurons during prion disease progression, allowing real-time monitoring of neurodegeneration caused by prion disease. Supported by the Public Health Agency of Canada.

P-45 characterIzatIon of vascular morphology and mechanIcal propertIes of mIddle cerebral ar-terIes In hypertensIve rats at rIsk for heart faIlure

C. Acosta1,3, C. M. Anderson1,4, and H. D. Anderson1,2,3 1Department of Pharmacology & Therapeutics, University of Manitoba; 2College of Pharmacy, University of Manitoba; 3Canadian Centre for Agri-Food Research in Health and Medicine, St. Boniface Hospital Research Centre; 4Neurosci-ence Research Program, Kleysen Institute for Advanced Medicine, Winnipeg Health Sciences Centre [email protected]”

Cerebral arteries undergo vascular remodeling and exhibit aberrant vascular compliance and dysfunction in hyper-tension. Hypertension is a significant independent risk factor for cognitive impairment and dementia, and is one of the primary causes for heart failure. Seventy-five percent of heart failure patients have antecedent hypertension and those at risk for heart failure are at greater risk of developing cognitive decline and eventual progression to Alzhei-mer’s dementia. We hypothesize that middle cerebral arteries of hypertensive rats at risk for heart failure undergo vascular remodeling, becoming less stiff and more compliant. Isolated and pressurized (30 mm Hg) middle cerebral arteries had external diameters that were smaller but not significantly different in spontaneously hypertensive heart failure (SHHF) rats (220±10 µm) than in age-matched SD rats (247±7 µm). Reduced lumen diameter and increased media width resulted in a significantly greater media-to-lumen ratio in SHHF (15.9 ± 2, p<0.05) than in age-matched SD (9±0.5). In SHHF, remodelling and growth indices were 58% and 43.6% respectively. Wall component stiffness was significantly higher in SHHF (18±3, p<0.0001) than in age-matched SD (6±0.9). Vascular compliance was significantly reduced in SHHF (0.12±0.03, p<0.001) versus age-matched SD (0.45±0.08). These results indi-cate that risk for heart failure in hypertension is associated with eutrophic vascular remodeling and altered vascular mechanics in middle cerebral arteries which may influence cerebral blood flow in SHHF. Supported by Research Mani-toba and the JG Fletcher PhD Fellowship in Functional Foods and Nutraceuticals. Supported by Research Manitoba and the JG Fletcher PhD Fellowship in Functional Foods and Nutraceuticals.


POSTER ABSTRACTS

P-46 InvestIgatIng dIagnostIc bIomarkers of fetal alcohol spectrum dIsorders (fasd) usIng em-bryonIc alcohol exposure In dIfferentIatIng neural stem cells

S. Amiri*1,2, K. Curtis1,2, C. O. Olson1,2, M. R. Del Bigio3, W. Xu2, G. Hicks1,2, J. R. Davie2, and M. Rastegar1 1Regenerative Medicine Program, University of Manitoba; 2Department of Biochemistry and Medical Genetics, Univer-sity of Manitoba; 3Department of Physiology & Pathophysiology, University of Manitoba [email protected]

Introduction: Fatal alcohol spectrum disorders (FASD) are one of the most prevalent neurodevelopmental challenges in the Western countries influencing 2-5% population in Canada. Focusing on the etiology of FASD, recent evidence suggests that epigenetic changes of neuronal stem cells (NSCs) during prenatal exposure to alcohol, mainly DNA methylation, play a pivotal role in pathophysiology of disease. Considering that the majority of patients with FASD (about 80%) exhibit no facial dysmorphic features, finding a reliable biomarker for early diagnosis of FASD may open new avenues for treatment strategies. Method: The aim of this current study is to establish and validate biological biomarkers through genome-wide RNA-seq study by qRT-PCR, Western blot, and ChIP studies in vitro, and in vivo FASD model systems, as well as human FASD samples (collaborations within a CIHR-funded team). Finally, using both in vivo and in vitro model systems, we will aim to identify and characterize methylation signatures relevant to clinical aspects of FASD. Results: Our previous results showed that continuous exposure to ethanol is able to alter the cell morphology and the expression of specific genes (Liyanage et al., 2015). Our genome wide RNA-seq studies indicate that morpholog-ical changes are associated with altered expression of some specific genes in the cortical areas of brain during devel-oping brain (Rastegar lab, unpublished data). We have shown the potential role of DNA methylation and Methyl CpG Binding Protein 2 (MeCP2) in alcohol-related neurological disorders, and will pursue it as a valid biological model for FASD in our future studies. Conclusion: Continuous exposure to ethanol during development of brain is associated with the alteration of cellular morphology and the deregulation of specific genes. Investigating the epigenetic marks on altered genes is expected in finding potential biomarkers for early diagnosis and treatment of FASD. Supported by Canadian Institute of Health Research (CIHR).

P-47 Involvement of autophagy In Increased temozolomIde-Induced apoptosIs by the addItIon of sImvastatIn In glIoblastoma cells

S. Shojaei*1, J. Alizadeh1, J. Thliveris1, N. Koleini2, E. Kardami1,2, S. Hombach-Klonisch1, T. Klonisch1, and S. Ghava-mi1 1Department of Human Anatomy and Cell Science, University of Manitoba; 2St-Boniface Hospital Albrechtsen Re-search Centre, University of Manitoba [email protected]

Temozolomide (TMZ) is commonly used as chemotherapeutic agent for Glioblastoma multiforme (GBM), the most common and aggressive brain tumor. Simvastatin (Simva) is a mevalonate (MEV) cascade inhibitor that can pass the blood brain barrier. Here, we studied the mechanism of sensitization of GBM cells to TMZ-induced apoptosis via sim-vastatin co-treatment in context of autophagy regulation. U251 and U87 (human GBM cells) were pretreated with low doses of Simva. (1 and 2.5 M) in the presence or absence of MEV (5 mM), CH (50 M), Farnesyl pyrophosphate (FPP) (15 M), Geranylgeranyl pyrophosphate (GGPP) (15 M) before treatment with TMZ (100 M) for 48-96h. Cell viability and apoptosis were evaluated by MTT assay and propidium iodide flow cytometry. Immunoblotting, immu-nocytochemistry and transmission electron microscopy were used to investigate the involvement of autophagy upon combination of Simva and TMZ treatment in GBM cells. We observed a significant increase in (P<0.01) TMZ-induced apoptosis in both U87 and U251 cells upon co-treatment with Simva. The increase in apoptosis was paralleled by a change in autophagy markers (LC3-βII, p62, and accumulation of double-membrane vacuoles) in Simva-TMZ treat-ed cells compared to TMZ alone. Effect of Simva was not reversed by addition of MEV, CH, FPP and GGPP (P>0.5). These results imply that Simva potentiates TMZ-induced apoptosis in GBM cells in a cholesterol independent manner possibly by modulating the autophagy pathway. Supported by Mitacs Accelerate PDF Foundation and Health Science Center Foundation.


POSTER ABSTRACTS

P-48 oxIdatIve modIfIcatIon of lysosomal enzymes holds the key In cross-talk betWeen protectIve autophagy and apoptotIc cell death

P. Nagakannan*, and E. Eftekharpour Department of Physiology and Pathophysiology, Spinal Cord Research Centre and Regenerative Medicine Program, University of Manitoba [email protected]

Rationale: Redox imbalance has been linked to wide range of neurological disorders such as traumatic and neurode-generative illnesses. Thioredoxin (Trx) is an endogenous thiol antioxidant defence system involved in redox homeo-stasis, and therefore has been shown to regulate vital processes including cell survival and death. Trx is inactivated by oxidation, which is rejuvenated by its reducing enzyme Thioredoxin Reductase (TrxR). Failure of Trx system is well documented in number of neurological disorders (ND) including Alzheimer’s disease. Autophagy (self-eating) is a protective mechanism under stress conditions responsible for sequestration and re-cycling of damaged materials in lysosomes. Although autophagy is commonly the first response of the cell, under prolonged or severe oxidative damage of proteins autophagy is replaced by apoptosis; a common mechanism of neuronal cell death in ND. The underlying molecular system controlling the autophagy-apoptosis switch remains to be identified. Hypothesis: Thioredoxin system plays a central role in regulation of autophagy-apoptosis interplay. Experimental Model: An in vitro model of neuronal starvation using SH-SY5Y cells was used. This model is widely used to study autophagy and apoptosis processes. Auranofin, a specific inhibitor of TrxR or genetic knockdown of TrxR was used to downregulate Trx system. Results: Exacerbation of oxidative stress after TrxR deficiency interrupted autophagy progression and promoted apoptosis. This was associated with decreased protein-degradation in lysosomes due to altered lysosomal acidifica-tion and accumulation of autophagosomes. We discovered that differential redox sensitivity of lysosomal proteases such as cathepsin B and L ensured the progression of apoptosis and disruption of autophagy. Pre-treatment with specific cathepsin B inhibitor in these conditions inhibited apoptosis and increased cell viability. Significance and Impact: This provides a novel mechanistic link between protein aggregation and oxidative stress and demonstrates for the first time that redox regulation of lysosomal cathepsins might be an important player in autophagy-apoptosis interplay. This opens a new avenue for developing novel therapeutic strategies for neurodegen-erative disease where lysosomes are dysfunctional. Supported by Research Manitoba (PN), HSCF, and the Canadian Paraplegic Association of Manitoba (EE).


POSTER ABSTRACTS

P-49 enhancIng chemotherapeutIc responses In cns malIgnancy through suppressIon of hyperac-tIve dna damage repaIr pathWays

M. Mostafizar*, and S. Katyal Department of Pharmacology & Therapeutics, University of Manitoba [email protected]

Introduction: We are targeting DNA repair pathways to enhance chemoradiotherapeutic strategies against medullo-blastoma (MB) and malignant glioma (MG), two highly invasive tumors of the central nervous system (CNS). Current methods to treat childhood medulloblastoma are highly intrusive and lead to poor quality of life while the three-year survival rate of patients afflicted with malignant glioma remains abysmal (<5%). Recurrence of these exceeding-ly malignant tumors is pervasive as they can adopt several mechanisms to resist anti-cancer therapeutics includ-ing activation and up-regulation of DNA repair pathways that act to resolve DNA damage elicited by radiation and chemotherapeutic agents (chemo-radiotherapy). DNA repair inhibitors like Poly (ADP-Ribose) Polymerase (PARPi), DNA-dependent protein kinase (DNA-PKi) and Ataxia Telengiectasia Mutated (ATMi) have shown promise to sensitize tumors to DNA damaging chemo-radiotherapeutics. In combination with anti-tumor agents, these sensitizers can significantly augment anti-cancer therapeutic success. However, differing tumors have variable expression/activity of these enzymes and their corresponding repair pathway(s), therefore; their identification, characterization and the development of strategies to modulate their expression can enhance current anti-tumor treatment efficacy. Objec-tive: To identify and inhibit specific DNA repair enzymes up-regulated in alternative compensatory repair pathways. Method: I will identify specific differentially-regulated DNA repair enzymes/pathways by gene expression meth-odology. From these findings, I will inhibit these DNA repair enzymes via shRNA or enzyme-specific inhibitors (if available), to chemosensitize MB and MG cells to DNA damaging therapeutics in an effort to reduce DNA repair in these cells thereby boosting tumor genotoxicity and cell death. Extent of DNA damage will be measured using novel high-throughput DNA repair assays combined with unique cellular DNA damage reporters/sensors to facilitate these studies. Result: In comparing subsets of MB and MG cell lines with existing DNA repair inhibitors, I have found differing DNA repair pathways as potential targets to sensitize these CNS tumors to chemoradiotherapeutics. MB cells rely on DNA-PK/SSBR-dependent pathways to resolve induced genotoxicity, while MG utilizes the ATM/SSBR pathways. Moreover from high-throughput comet assay data, drug-mediated tumor cell death was enhanced in MB cell lines (DAOY & D283) co-treated with PARPi, PARPi+DNAPKi and/or PARPi+ATMi. Resolution of Topoisomerase 1 (Camptothecin/Topotecan) DNA damage was found to be primarily PARP/SSBR dependent whereas both PARP1/SSBR and DSBR pathways resolve DNA alkylation (Methymethanesulfonate, MMS) damage in MB. These data are consistent with cell death assays. Furthermore analyses of Hela and Human Fibroblast lines revealed that the effects of the above treat-ment groups is tumor specific. Future work includes detailed comparative analysis using the above treatment combinations, to identify specific highly active tumor-specific DNA repair enzymes with enhanced tumor cell death. These include the use of “DNA damage repair response” PCR arrays to compare the expression levels of individual DNA repair enzyme/pathway members in medulloblastoma. Conclusion: I have identified unique DNA repair enzymes/pathways, which may mediate specific differential che-mo-radioresistant phenotypes in MB and MG. An expanded analysis is currently underway to further differentiate DNA repair mechanisms and therapeutic responses. I hope to translate these findings into pre-clinical models where-by my data may lead to identifying next-generation brain cancer treatments with improved patient survival and quality-of-life.


POSTER ABSTRACTSP-50 characterIzatIon of a neural cIrcuIt In a mouse model of schIzophrenIa

B. Karimi*, and T. J. Siddiqui Department of Physiology and Pathophysiology, University of Manitoba; Neuroscience Research Program, Kleysen Institute for Advanced Medicine, Winnipeg Health Sciences Centre [email protected]

The medio-dorsal nucleus of thalamus (MDN) is implicated in variety of cognitive tasks including memory, social interaction and decision-making. MDN sends projections to prefrontal cortex (PFC), amygdala, nucleus accumbens and hippocampus and receives projections from these areas as well. The MDN-PFC circuit has been suggested to be disrupted in schizophrenia. The synapse organizing protein, Leucine Rich Repeat Transmembrane Neuronal protein 1 (LRRTM1), is expressed at very high levels in the MDN. Genetic association studies show that that ¬Lrrtm1 is strongly associated with schizophrenia. We hypothesize that LRRTM1 controls excitatory synaptic transmission in the MDN and modulates excitatory drive to the PFC. We propose that targeted deletion of LRRTM1 in the MDN will reduce excitatory synaptic function in that region and alter cognition. To test this hypothesis, we have selectively knocked out (KO) Lrrtm1 together with another family member, Lrrtm2 in the MDN of adult floxed mice. Mice lacking LRRTM1 and LRRTM2 selectively in the MDN display altered behaviour. Ongoing studies will reveal whether synapse numbers and function are altered in the MDN. These studies indicate the importance of studying the functions of synapse organizing defined neural circuits. Supported by CIHR.

P-51 the regulatIon of nmdar and mglur5 by mIcrorna-128-3p WIth relevance to neurode-generatIve dIsease

A. S. Boese1,2, A. Patterson1, K. J. Manguiat1, A. Majer1, and S. A. Booth1,2 1Department of Medical Microbiology & Infectious Diseases, University of Manitoba; 2Zoonotic Diseases and Special Pathogens,Public Health Agency of Canada [email protected]

Objective: To identify the functional targets of microRNA-128-3p, a miR that is deregulated in multiple CNS neurode-generative diseases. Methods: First, the deregulation of miR-128-3p in CA1 neurons during RML Scrapie prion disease was identified using laser capture microdissection and real time PCR. Bioinformatic analysis was performed using miR-mRNA pre-diction algorithm TargetScan Human 7.1 to determine neuronal 3`UTR targets, which were validated by Luciferase Reporter Assay. The glutamate signaling pathways were manipulated in murine primary hippocampal neurons (hcc) to study the effects on miR-128-3p expression. Finally, miR-128-3p gain of function experiments were performed in hcc to determine effects on 1) mRNA targets using realtime PCR and 2) protein changes using mass spectrometry. Results: In the CA1 hippcampal neurons, miR-128-3p is upregulated during early RML Scrapie and downregulated at symptomatic stages of disease. The predicted 3` UTR targets of GRIN2B, GRIN2D, and GRM5 were validated by Luciferase assays, and GRIN2D and GRM5 mRNA decreased during gain of function studies. In hcc, chronic synaptic and extrasynaptic NMDAR activation resulted in miR-128-3p reduction. Finally, the proteomic targets of miR-128-3p remained elusive as only 1 protein, SLIT3, was identified as downregulated by tandem mass spectrometry in miR-128-3p gain of function experiments in hcc. Conclusions: In hcc, mRNA encoding glutamate receptor subunits GRIN2B, GRIN2D, and GRM5 are regulated by miR-128-3p and glutamate signaling overactivation results in miR-128-3p downregulation.


POSTER ABSTRACTSP-52 menstrual cycle mood changes detected WIthIn evestg recordIngs

B. Lithgow* Riverview Health Centre [email protected]

Introduction: There are ample evidences women of childbearing age experience mood changes consequent to their menstrual cycle. Objective: Previous Electrovestibulography (EVestG) studies demonstrated an ability to detect depression and mea-sure its severity. The hypothesis tested was that ‘mood’ changes consequent to the menstrual cycle could be detect-ed within EVestG recordings. Methods: EVestG recordings were made on 12-15 females during their Menstrual cycle. One in days 1-4 post luteal, one in the follicular phase and one in the luteal phase. These were examined for separation. Results: The Luteal and Follicular phases were separately classified with 96% accuracy using a leave one out cross validation method. Conclusion: There appears a measurable physiological change using EVestG in Luteal versus Follicular phase women. Supported by Neural Diagnostics.


AUTHOR INDEXAcosta, C P-45Adlimoghaddam, A P-5, P-6Aghanoori, M P-4Albensi, BC P-5, P-6, P-9Alhindi, A P-10Alizadeh, A P-2, P-13, P-36, P-47Aljuaid, M P-3, P-10, P-31Amiri, S P-46Anderson, CM P-19, P-21, P-43, P-45Anderson, HD P-45Armstrong, K P-11, P-34Ashtari, N P-27, P-32Aulston, B P-25Bamji, S P-43Basalah, D P-7Beiko, J P-38Belrose, JC P-22Bergen, H P-38Bharti, V P-20Bhullar, PK P-34, P-39Boese, AS P-51Booth, SA P-44, P-51Borys, A P-10, P-31Braun, K P-8Buist, R P-24, P-28Bybel, B P-3Caetano, F P-22Calcutt, NA P-4Champagne-Jorgensen, K P-37Chen, X P-34Chowdhury, SR P-4, P-9, P-19Chudley, AE P-7Courtney, SM P-42Curtis, K P-46Davie, JR P-7, P-46Del Bigio, MR P-7, P-35, P-46Dhume, S P-37, P-40Djordjevic, J P-9Dong, X P-41Douville, RN P-18Dyck, SM P-1, P-33, P-36Eftekharpour, E P-48Ferguson-Parry, J P-18Fernyhough, P P-4, P-9, P-19Figley, CR P-10, P-42Gangadharappa, H P-22Ghavami, S P-38, P-47Globa, A P-43Glogowska, A P-38Goertzen, AL P-3, P-31Hart, CG P-33Henrie, R P-13Herrera, SL P-24, P-28Hicks, G P-46Hobson, DE P-10, P-31Hogan-Cann, A P-43Hombach-Klonisch, S P-38, P-47

Jackson, MF P-12, P-22, P-23, P-29, P-30Jarmasz, JS P-7Jiao, X P-27, P-32Johnston, ML P-22Kamboj, A P-19Kardami, E P-47Karimi, B P-50Karimi-Abdolrezaee, S P-1, P-2, P-13, P-33, P-36Katako, A P-3, P-26, P-31Kataria, H P-1, P-2, P-13, P-33, P-36Katyal, S P-49Kauppinen, TM P-8, P-14, P-30Kim, JH P-8, P-14Kirouac, GJ P-26, P-41Klonisch, T P-38, P-47Ko, JH P-3, P-10, P-26, P-31Koleini, N P-47Kornelsen, J P-16Krcek, J P-38Lang, B P-1Lavine, N P-12, P-22, P-23, P-29Levin, D P-3Li, S P-26, P-41Lithgow, B P-52Lu, L P-21, P-43Lu, P P-19, P-21Lynn, B P-39MacDonald, JF P-22Majer, A P-51Manghera, M P-18Manguiat, KJ P-51Mao, X P-35Martin, MJ P-24, P-28, P-44Marzban, H P-27, P-32Matsuda, KM P-24, P-28Mercredi, ME P-24, P-28Mostafizar, M P-49Nagakannan, P P-48Nagra, G P-35Nagy, JI P-39, P-43Natarajan, S P-38Nazzal, M P-34Nguyen, D P-36Odero, G P-14Olson, CO P-46Parkinson, TD P-16Patil, C P-29Patterson, A P-51Perez, C P-9Pitz, M P-38Raghunatha, P P-30Rahimi-Balaei, M P-27, P-32Rastegar, M P-7, P-46Rezaeian Mehrabadi, A P-8, P-14Rizi, SS P-13Rommel, A P-38Roppongi, RT P-37


AUTHOR INDEXRyner, L P-10, P-31Sabbir, MG P-4Santhosh, KT P-1, P-2, P-13, P-33, P-36Shahriary, GM P-2, P-13Shelton, P P-3Shojaei, S P-47Siddiqui, TJ P-37, P-40, P-50Silver, J P-1Smith, DR P-4Smith, SD P-16Snow, WM P-9Solar, K P-10, P-15Stecina, K P-34, P-39Stevenson, M P-30Tan, H P-17Tanwar, S P-12Tessler, L P-8, P-14Thanasupawat, T P-38Thliveris, J P-47Uddin, MN P-42Verma, IM P-38Wang, J P-17, P-20Wang, Y P-17, P-37Wang, Yiran P-17Williams, K P-31Xie, Y P-23Xu, W P-46Yeung, A P-23Zhang, D P-26


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