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Neurotransmitter (NTs)

Department of PhysiologySchool of Medicine

University of Sumatera Utara

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Introduction:

The Nervous System is incrediblycomplex and contains manyimportant chemical messengerscalled neurotransmitters

Neurotransmitters are aminoacid based molecules thatrelay signals between majorsystems of the body.

Neurotransmitters define ourmoods, actions, and health

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Introduction:

The importance of themtranscends their role in thebrain. They act as messengersbetween the: immune,endocrine, digestive, and

nervous system. They are present throughout

the body and required forproper brain and bodyfunctions. The brain uses

neurotransmitters to tell yourheart to beat, your lungs tobreathe, and your stomach todigest

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Introduction:

Neurotransmitters are also

necessary for memory and

thinking, feeling, sleeping,

and your energy. Scientific literature has

established the link

between neurotransmitter

imbalances and clinicalsymptoms

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Some symptoms of NeurotransmitterImbalance

Stress, anxiety, mood swings, depression,irritability, agitation, apathy, panic attacks,difficulty concentrating, developmentaldelays, attention issues, memory decline,

sleep disturbances, headaches, weightissues, food (carbohydrate) cravings,fatigue, addiction, decreased sex drive,hormonal imbalance & PMS, digestive

troubles, autism, and immune systemproblems

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Neurotransmitter Imbalance

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The synthesis of neurotransmitters

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The synthesis of neurotransmitters

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Functional Classification of

Neurotransmitters (NTs)A. Based on effects

excitatorycause depolarization (glutamate)

inhibitorycause hyperpolarization (GABA)

effect of some depends on postsynapticmembrane receptors ACh and NE have different receptor typessome

that cause excitation and other types that causesinhibition

B. Based on mechanism of action direct (channel-linked receptors)

indirect (G protein-linked receptors = secondmessenger system)

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Modes of Action: Direct Action

open ion channels immediate and localized

action

action depends on binding

of NT to receptors followedby channel activation, ion

influx and membrane

potential changes

excitatory examples:

aspartate, acetylcholine

(ACh), glutamate, ATP

*open Na+/K+, Ca2+

channels leading to

depolarization

inhibitory examples:

gamma aminobutyric acid

(GABA), glycine

*open Cl- or K+ channels

leading to

hyperpolarization

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Modes of Action: Indirect Action

slower, longer-lasting effects work through second messengers

binding of NT with receptor activates Gprotein in membrane which works through

cyclic AMP (cAMP = second messenger) to: regulate ion channels (open or close)

activate kinase enzymes within cytoplasm

(activate proteins in cytoplasm)

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Modes of Action: Indirect ActionExamples

Biogenic amines (dopamine, norepinephrine, epinephrine)

Peptides (endorphins, dynorphins, substance P)

ACh (at muscarinic receptors)

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Structural Classes of Neurotransmitters

Classified according to chemicalstructure:

Acetylcholine (ACh)

Biogenic Amines

Amino Acids

Peptides

Novel Messengers

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Acetylcholine (ACh)

first NT to be discovered

excitatory to skeletal muscles

excitatory/inhibitory to viscera

found in CNS and PNS (NMJ with skeletal

muscle, NEJ for parasympathetic nervous

system)

formed from acetyl-CoA and choline

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Acetylcholine (ACh)

degraded by acetylcholinesterase (AChE)

Myasthenia gravis - autoimmune disorder

of skeletal muscle ACh receptors

Alzheimers disease - decreased ACh level

in brain that ultimately results in mentaldeterioration

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Biogenic Amines

synthesized from amino acid tyrosine

found in CNS and PNS

catecholamines norepinephrine [NE], epinephrine, dopamine,

excitatory or inhibitory

indolamines seratonin and histamine

generally inhibitory

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Biogenic Amines

play role in emotional behavior and helpregulate biological clock; norepinephrineis main NT of sympathetic division of ANS

schizophrenia - overproduction ofdopamine

Parkinsons disease - deficient dopaminein basal ganglia

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Amino Acids & Peptides

Amino Acids GABA = gamma amino butyric acid (principal

inhibitory NT in brain),

glycine (generally inhibitory NT, in spinal cord),

glutamate (CNS, excitatory) Peptides (Neuropeptides)

strings of amino acids produced in CNS andPNS:

endorphins and enkephalins (natural opiates)

substance P (mediator of pain signals)

some also produced by nonneural tissues (e.g.,cells of GI tract - somatostatin, cholecystokinin,vasoactive intestinal peptide [VIP])

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Novel Messengers

Neurotransmitters that dont fit other

categories

NO = nitric oxide

involved in long-term synaptic potentiation(learning and memory)

relaxation of intestinal smooth muscles

responsible for brain damage in stroke

patients

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Novel MessengersNeurotransmitters that dont fit other

categories ATP = adenosine triphosphate

promotes synthesis and uptake of other NTs inCNS and PNS

CO = carbon monoxide

enhances neurotransmission in some circuitsinvolved in logic

regulator of cyclic GMP (second messenger)

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Termination of NT Effects

1. removal from cleft by reuptakeinto astrocytes or presynapticmembrane (e.g., norepinephrine)

2. degradation of NT by enzymespresent in postsynaptic membraneor synaptic cleft

e.g., acetylcholine [ACh] degradedby the enzyme acetylcholinesterase -[AChE]

3. diffusion away from cleft

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Causes Neurotransmitters to be out ofbalance

chronic stress,

poor dietary habits,

neurotoxins,

genetics.

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Some symptoms of NeurotransmitterImbalance ; chronic stress

the primary contributor toneurotransmitter imbalance. Stress,both emotional and physical, cancause neurons to use up largeamounts of neurotransmitters to helpus cope with the situation

Chronic daily stress, from a busy

career, a stressed relationship, or abacterial or viral infection, will tax thenervous system, and over time,deplete neurotransmitter supplies

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Some symptoms of NeurotransmitterImbalance; poor dietary habits

Diets with insufficient proteins ortoo many high glycemiccarbohydrates will increase

excretion of neurotransmitters Also, diets low in Omega-3 fatty

acids will lead to poor neuronfunction because our brain cell

membranes are composedprimarily of lipids and Omega-3fats help to stabilize thesemembranes

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Some symptoms of NeurotransmitterImbalance; neurotoxins

There are a vast amount of

environmental toxins, not to

mention the use of alcohol,nicotine, and caffeine that also

affect brain chemistry and nervous

system health.

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Some symptoms of NeurotransmitterImbalance; genetics

Some individuals are metabolically

predisposed to neurotransmitter

deficiencies or excesses. Certainhealth conditions, such as depression

and attention deficit/hyperactivity

disorder, are found to run in families