H2020Индивидуална стипендия2019–2021

ALCO-ADO · Unveiling the alcohol-dependent alterations in local dendritic translation of mRNAs in the prefrontal cortex during adolescence

„Хоризонт 2020“ — Действия „Мария Склодовска-Кюри“

Период: 2019-04-01 → 2021-03-31
Финансиране от ЕС: 178 320 €
Участници: 1
Схема: MSCA-IF-EF-RI

Линиите свързват координатора с партньорите.

Накратко на български

Консумацията на алкохол в тийнейджърските години променя развитието на префронталния кортекс и синтеза на протеини в неговите клетки. Разбирането на тези процеси и разликите между половете помага за търсенето на нови методи за лечение на алкохолната зависимост.

Този кратък обзор е генериран от изкуствен интелект

Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.

Резултати накратко

Unveiling the alcohol-dependent alterations in local dendritic translation of mRNAs in the prefrontal cortex during adolescence

Alcohol use disorder (AUD) is a devastating relapsing disease which represents the fourth leading cause of preventable death worldwide. AUD has been considered as a pathological condition that develops in adulthood, but emerging evidence suggest that the roots of alcohol addiction begin to grow earlier in life, precisely during adolescence. Indeed, studies have suggested that heavy alcohol intake perturbs the maturation of the adolescent brain, inducing neuroadaptations that in turn increase the risk for developing AUD and comorbid psychopathology later in life. In addition, the historic gender gap in AUD, characterized by a greater prevalence in men, has been narrowing over the past years, highlighting the importance of understanding sex differences in the biology and treatments of AUD. However, the current literature on sex differences in the etiology of AUD is still very limited. The long-term objectives of this research are (i) to unveil how alcohol consumption during adolescence alters brain maturation and leads to long-lasting behavioral impairments, (ii) to reveal how alcohol differentially impacts male and female brain maturation; (iii) to identify new mechanisms and targets of alcohol’s actions in order to develop new therapies for treating AUD. Conclusions of the action We showed that voluntary alcohol binge-drinking during adolescence induces delayed appearance of behavioral defects in both sexes (Van Hees et al, under review, https://doi.org/10.1101/2020.08.11.245878). Moreover, our preliminary results suggest that AAE may modulate the activity of local translation regulators and interferes with PFC maturation.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз

Цел на проекта

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.

Оригинален текст от CORDIS (на английски).

Участници

UNIVERSITE DE LIEGE · LIEGEКоординаторБелгия