Description du projet
Le cerveau adolescent et l’alcool
L’alcool a plus de répercussions sur les adolescents que sur les adultes, car leurs cerveaux sont toujours en cours de développement. La recherche a démontré que les cerveaux en développement sont plus enclins à la dépendance. En outre, l’alcool entrave le développement cérébral. Par exemple, une consommation excessive d’alcool affecte le cortex préfrontal du cerveau, impliqué dans la planification du comportement cognitif complexe, l’expression de la personnalité, la prise de décision et la modération du comportement social. Le projet ALCO-ADO, financé par l’UE, entend découvrir comment l’alcool module la traduction locale des protéines synaptiques dans le cortex préfrontal durant l’adolescence. Il cherchera également à identifier les ARNm synaptiques cibles et à analyser leur implication dans la plasticité synaptique altérée sous-jacente aux comportements anormaux dépendants de l’alcool.
Objectif
During adolescence, the brain undergoes intense maturation, particularly in the frontal areas. The prefrontal cortex (PFC) is implicated in executive functions, and its immaturity in adolescents is associated with increased impulsivity and heightened vulnerability to deleterious effects of drugs. Alcohol is the most consumed drug among adolescents, and its excessive consumption profoundly impairs PFC function, leading to long-lasting defective behaviors, psychological problems and neurocognitive defects. However, the precise mechanisms underlying alcohol-induced alterations in PFC maturation remain poorly understood. Alcohol addiction is considered being a maladaptive form of learning and memory, as alcohol usurps the molecular mechanisms underlying those processes, such as long-lasting synaptic plasticity. Long-lasting changes in the strength of synaptic connections mainly depend on the local translation of mRNAs at synaptic sites. It has been shown that alcohol modifies synaptic proteins composition by modulating the activity of key translation regulators, such as mTORC1 and eIF2α, in brain regions associated with the mesocorticolimbic pathway. Here, we propose to analyze the alcohol-dependent modifications of the synaptic translatome of specific neuronal populations (glutamatergic neurons and GABAergic interneurons) in the PFC of adolescent male and female mice, by using a multidisciplinary approach combining biochemistry, imaging, electrophysiology and behavioral tests. This project aims to uncover how alcohol modulates local translation of synaptic proteins in the PFC during adolescence, to identify the targeted synaptic mRNAs and analyze their involvement in altered synaptic plasticity underlying alcohol-dependent defective behaviors. In addition, this project aims at identifying the differential sensibility to alcohol’s effects between males and females as well as the differences in behavioral consequences.
Champ scientifique
Programme(s)
Régime de financement
MSCA-IF-EF-RI - RI – Reintegration panelCoordinateur
4000 Liege
Belgique