il ruolo del nerve growth factor (ngf) nello stress e...
TRANSCRIPT
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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])
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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.
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NERVE GROWTH FACTOR exerts thefollowing actions:
- TROPIC
- DIFFERENTIATIVE
- TROPHIC
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Rita Levi-Montalcini and Luigi Aloe
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SOCIAL INTERACTIONS ANDAGGRESSIVE BEHAVIOR
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SOCIAL INTERACTIONS ANDAGGRESSIVE BEHAVIOR
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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*In developing rats unpublished observations indicate a decrease of NGF level and NGF receptor expressionin the striatum following cold-water swimming stress while an increase was shown in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.
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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)
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Brigata Paracadutisti "Folgore"
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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
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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
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LONG-TERM EFFECTS OF EARLY SOCIAL EXPERIENCE
- adult social behaviour
- brain neurotrophin levelsNGF and BDNF levels
social/agonistic behaviour
- early social enrichment
communal nesting
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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
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MOTHER-OFFSPRING INTERACTION
licking and grooming
nursing
retrieving
Nelson, 1995
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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 ?
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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)
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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
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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
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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
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* 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
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CN mice display higher propensity to interact socially
nose sniffing
ADULT SOCIAL BEHAVIOUR
Branchi et al, Biol Psychiatry, 2006
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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
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(SOCIAL) STRESS
(SOCIAL) COPING
RENEWED BRAIN PLASTICITY
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ENHANCED VULNERABILITY TODEPRESSION (MOOD DISORDERS)
“PARA”PHYSIOLOGICALGROWTH FACTOR(S) LEVELS
NGF for what ? BDNF for what ?
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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
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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
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NGF, NEUROTROFINE E
RIABILITAZIONE NEURO-MOTORIA:
prospettive per una interazione tra
l’Istituto Ortopedico Rizzoli
e l’Istituto Superiore di Sanità