Descripción del proyecto
El encéfalo adolescente y el alcohol
El alcohol tiene un mayor efecto sobre los adolescentes que sobre los adultos porque el encéfalo de los primeros todavía se está desarrollando. Las investigaciones han demostrado que los encéfalos en desarrollo son más propensos a la adicción. Es más, el alcohol altera el desarrollo del encéfalo. Por ejemplo, un consumo excesivo de alcohol afecta el córtex prefrontal, que interviene en la planificación cognitiva compleja, la expresión de la personalidad, la toma de decisiones y la moderación del comportamiento social. El proyecto ALCO-ADO, financiado con fondos europeos, tiene como objetivo descubrir cómo el alcohol modula la traducción local de proteínas sinápticas en el córtex prefrontal durante la adolescencia. Además, intentará identificar los ARNm sinápticos específicos y analizará su implicación en la plasticidad sináptica alterada subyacente a comportamientos anormales dependientes del alcohol.
Objetivo
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.
Ámbito científico
Programa(s)
Régimen de financiación
MSCA-IF-EF-RI - RI – Reintegration panelCoordinador
4000 Liege
Bélgica