MATRIXRESILIENCE

Role of hevin in the neuroplasticity of stress-related disorders and addiction

Coordinatore	UNIVERSITE PIERRE ET MARIE CURIE - PARIS 6    more  Organization address address: Place Jussieu 4 city: PARIS postcode: 75252 contact info Titolo: Ms. Nome: Lucie Cognome: Salvaudon Email: send email Telefono: 33144277279
Nazionalità Coordinatore	France [FR]
Totale costo	100˙000 €
EC contributo	100˙000 €
Programma	FP7-PEOPLE Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013)
Code Call	FP7-PEOPLE-2013-CIG
Funding Scheme	MC-CIG
Anno di inizio	2013
Periodo (anno-mese-giorno)	2013-09-01   -   2017-08-31

 Partecipanti

#	participant	country	role	EC contrib. [€]
1	UNIVERSITE PIERRE ET MARIE CURIE - PARIS 6  Organization address address: Place Jussieu 4 city: PARIS postcode: 75252 contact info Titolo: Ms. Nome: Lucie Cognome: Salvaudon Email: send email Telefono: 33144277279	FR (PARIS)	coordinator	100˙000.00

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 Obiettivo del progetto (Objective)

'Matricellular proteins mediate interaction between cells and the extracellular matrix and are essential regulators of synaptic function and architecture. Recently, the two prototypical matricellular proteins SPARC and hevin have been implicated in depression-like behaviors, antidepressant response and resilience to stress. I found that hevin is induced by chronic social stress in the nucleus accumbens (NAc), a key brain reward region, only in resilient individuals. Importantly, its overexpression in susceptible mice could reverse social avoidance. This key observation, along with other evidence supporting a role for hevin in synaptogenesis and its presence at excitatory synapses, suggests that hevin is involved in the neuroplasticity underlying positive affect and motivation. My main objective is to define the role of hevin in the adatation to stress and drugs of abuse. I plan to combine my expertise in rodent behavior, neuroanatomy, pharmacology, molecular biology and viral-mediated gene transfer to first determine in which cell type hevin is induced in the NAc plays a role in resilience. I will manipulate hevin in selective cells using Cre transgenic mice and flox-STOP viruses in order to test whether it is required for resilience and antidepressant treatment in these cells. In the second aim, I will extend this anatomical and functional approach to study other emotionally-related behaviors, in particular in response to cocaine. I will also study the effect of hevin manipulation on dendritic spine morphology. Third, I will determine the mechanism controlling and regulating hevin in primary neuronal cultures. Last, I will identify hevin binding partners through co-immunoprecipitation and proteomics. This focus of research is particularly novel and promising, and is expected to bring benefit for psychiatric disorders such as depression and addiction, in addition to fundamentally advancing the field of neuronal plasticity, hence the neural basis of learning and memor'