Reparto di Neuroscienze comportamentaliDipartimento di Biologia cellulare e NeuroscienzeIstituto Superiore di Sanità
IL RUOLO DEL NERVE GROWTH FACTOR (NGF)NELLO STRESS E COPING
DEI RODITORI E DELL’UOMO
Enrico Alleva ([email protected])
First, it is impossible to think effectively aboutdepression outside the context of biology.Second, it is impossible to think effectively aboutdepression as only being a matter of biology.Finally, despite the vast quantities of excellentresearch on which those two conclusions rest, weremain woefully inadequate at effectively treatingdepression in vast numbers of its sufferers.
NERVE GROWTH FACTOR exerts thefollowing actions:
- TROPIC
- DIFFERENTIATIVE
- TROPHIC
Rita Levi-Montalcini and Luigi Aloe
SOCIAL INTERACTIONS ANDAGGRESSIVE BEHAVIOR
SOCIAL INTERACTIONS ANDAGGRESSIVE BEHAVIOR
BEHAVIOURAL “STRESS SYNDROMES”EITHER PRODUCING OR NOT PRODUCING NGF RELEASE
INTO THE BLOODSTREAM
NON- PSYCHOSOCIALInescapable footshock NOEscapable footshock NOCold water swimming NO*Restraint stress NOForced biting NO
PSYCHOSOCIALMale fighting YES (high, < 100-300 ng/ml serum >)Female fighting YES (low, < 3-13 ng/ml serum >)Pre-copula arousal (F) YES (low, < 2-9 ng/ml serum >)
*In developing rats unpublished observations indicate a decrease of NGF level and NGF receptor expressionin the striatum following cold-water swimming stress while an increase was shown in the hippocampus.
Alleva E, Aloe L (1989) Physiological roles of nerve growth factor in adult
rodents: a biobehavioral perspective. Int J Comp Psychol 2:213-230
“Hypothalamic NGF release
could also play a crucial role
in linking the "emotional"
status caused by a
psychosocial stressor and
the biological needs of the
organism (and of its brain) to "remember" the events leading
to an appropriate (or inappropriate) coping with the stressor
itself”(p. 223)
Brigata Paracadutisti "Folgore"
ACTH AND NGF LEVELS IN THE BLOOD OFPARACHUTISTS BEFOREAND AFTER JUMPING
Aloe L. et al. (1994) Proc Natl Acad Sci USA
0
20
40
60
80
AC
TH
, p
g/m
l
NG
F, p
g/m
l0
150
100
50
controls before jump after jump
PassionateLoveScale
ROMANTIC LOVE and NGF
Romantic love induces an increase of circulating NGF (160-170% of basallevels) lasting about a year
Emanuele et al. Psychoneuroendocrinology 2006
LONG-TERM EFFECTS OF EARLY SOCIAL EXPERIENCE
- adult social behaviour
- brain neurotrophin levelsNGF and BDNF levels
social/agonistic behaviour
- early social enrichment
communal nesting
MOTHER-OFFSPRING INTERACTION
The mother is the mostpervasive, powerful andleast understood sourceof early experience forthe mammalian infant
Basic physiological sy-stems are regulated bythe mother, includingbrain development
MOTHER-OFFSPRING INTERACTION
licking and grooming
nursing
retrieving
Nelson, 1995
MOTHER-OFFSPRING INTERACTION
effects on physiology and behaviour of adult offspring- Seymour ‘Gig’ Levine (University of Stanford)- Michael Meaney (McGill University)
maternal behaviour of the female offspring
Capone, Bonsignore,and Cirulli, 2005,Current Protocols inToxicology
coping response to stress
social behaviour
emotional response
cognitive abilities ?
EARLY MANIPULATION: COMMUNAL NESTING
Communal nesting (CN): three mothers keep their pups together in a single andshare care-giving behaviour from birth to weaning (postnatal day 25)
compared to standard nesting laboratory condition (SN)
COMMUNAL NESTING: MATERNAL BEHAVIOUR
higher levels of maternalcare were shown under CN
### = p < 0.001, CN vs. SN mice. n = 8for each group. Data are means ± S.E.M
arched back nursingBranchi et al, Biol Psychiatry, 2006
SN mice learn session after session to play their social role
ADULT SOCIAL/AGGRESSIVE BEHAVIOUR
1 3 5day
1 3 5day
ATTACK
Branchi et al, Biol Psychiatry, 2006
CN mice show higher social competencies, playing morepromptly a social role
** = p < 0.01 vs. the relative SN group (i.e., either dominants orsubordinates
ADULT SOCIAL/AGGRESSIVE BEHAVIOUR
1 3 5day
1 3 5day
ATTACK
Branchi et al, Biol Psychiatry, 2006
* and ** = respectively p < 0.05 and < 0.01 vs. the relativeSN group (i.e., either dominants or subordinates); ### =respectively p < 0.001, CN vs. SN mice
ADULT SOCIAL/AGGRESSIVE BEHAVIOUR
Branchi et al, Biol Psychiatry, 2006
CN mice display higher propensity to interact socially
nose sniffing
ADULT SOCIAL BEHAVIOUR
Branchi et al, Biol Psychiatry, 2006
NEUROTROPHIN LEVELSBrain neurotrophin levels are modulated by early and/or adult social experiences
** and *** = respectively p <0.01 and < 0.001 vs. SN mice.$, $$ and $$$ = respectively p< 0.05, p < 0.01 and < 0.001vs. same nesting conditiondominant mice. ## and ### =respectively p < 0.01 and <0.001, CN vs. SN mice
Branchi et al, Biol Psychiatry, 2006Branchi et al, J Neurosci Res, 2006
(SOCIAL) STRESS
(SOCIAL) COPING
RENEWED BRAIN PLASTICITY
ENHANCED VULNERABILITY TODEPRESSION (MOOD DISORDERS)
“PARA”PHYSIOLOGICALGROWTH FACTOR(S) LEVELS
NGF for what ? BDNF for what ?
Aloe L, Bracci-Laudiero L, Alleva E, Lambiase A, Micera A, Tirassa P (1994) Emotionalstress induced by parachute jumping enhances blood nerve growth factor levelsand the distribution of nerve growth factor receptors in lymphocytes. Proc NatlAcad Sci U S A 91:10440-10444.
Aloe L, Tuveri MA, Guerra G, Pinna L, Tirassa P, Micera A, Alleva E (1996) Changes inhuman plasma nerve growth factor level after chronic alcohol consumption andwithdrawal. Alcohol Clin Exp Res 20:462-465.
Emanuele E, Politi P, Bianchi M, Minoretti P, Bertona M, Geroldi D (2005) Raisedplasma nerve growth factor levels associated with early-stage romantic love.Psychoneuroendocrinology.
Hadjiconstantinou M, McGuire L, Duchemin AM, Laskowski B, Kiecolt-Glaser J, GlaserR (2001) Changes in plasma nerve growth factor levels in older adults associatedwith chronic stress. J Neuroimmunol 116:102-106.
Lang UE, Gallinat J, Kuhn S, Jockers-Scherubl C, Hellweg R (2002) Nerve growthfactor and smoking cessation. Am J Psychiatry 159:674-675.
Luppi P, Levi-Montalcini R, Bracci-Laudiero L, Bertolini A, Arletti R, Tavernari D,Vigneti E, Aloe L (1993) NGF is released into plasma during human pregnancy:an oxytocin-mediated response? Neuroreport 4:1063-1065.
PSYCHOSOCIAL STRESS INCREASES CIRCULATING NGF LEVELS
Alleva E, Francia N (2009) Psychiatric vulnerability: suggestions from animal modelsand role of neurotrophins. Neurosci Biobehav Rev 33:525-536.
Cirulli F, Alleva E (2009) The NGF saga: From animal models of psychosocial stress tostress-related psychopathology. Front Neuroendocrinol. in press
PSYCHOSOCIAL STRESS INCREASES CIRCULATING NGF LEVELS
Recent Reviews
NGF, NEUROTROFINE E
RIABILITAZIONE NEURO-MOTORIA:
prospettive per una interazione tra
l’Istituto Ortopedico Rizzoli
e l’Istituto Superiore di Sanità