# Regional and temporal dynamics of DNA methylation and epigenetic gene regulation in response to binge-like alcohol exposure in the adolescent mouse brain

## TL;DR

This study shows how binge drinking during adolescence affects DNA methylation and gene regulation in different brain regions of mice, potentially leading to long-term cognitive and behavioral issues.

## Contribution

The study reveals region-specific and time-dependent epigenetic changes in the adolescent mouse brain due to binge-like alcohol exposure.

## Key findings

- Binge-like alcohol exposure in adolescent mice causes oxidative damage and alters DNA methylation and gene expression in brain regions.
- The prefrontal cortex shows persistent upregulation of DNA methylation genes, which may impair executive functions.
- The hippocampus exhibits decreased DNA methylation, potentially leading to memory and learning impairments.

## Abstract

Adolescence is a critical late phase of the neurodevelopment, characterized by marked brain plasticity and increased vulnerability to environmental challenges such as alcohol exposure. This study examined the impact of binge-like alcohol exposure in male Swiss Webster mice, focusing on oxidative damage, epigenetic and transcriptional alterations in key brain regions, such as the prefrontal cortex, cerebellum, striatum and hippocampus. Our results demonstrated that acute alcohol exposure during adolescence induces oxidative damage with significant alterations in global DNA methylation and gene expression involved in epigenetic regulation with distinct temporal and anatomical profiles. In the prefrontal cortex binge-like alcohol exposure exhibited persistent upregulation of genes associated with DNA methylation and histone deacetylation, consistent with prolonged transcriptional silencing that may impair executive functions and decision-making. The hippocampus appeared particularly sensitive, exhibiting marked decreases in DNA methylation and gene expression changes associated with an open chromatin state leading potentially linked to cognitive impairments in memory and learning impairments in memory and learning. In the striatum, binge-like alcohol exposure induced active DNA demethylation and transient modulation of histone methyltransferases, reflecting a dynamic compensatory response to alcohol-induced transcriptional repression, with implications for reward processing and impulse control. Similarly the cerebellum displayed a biphasic transcriptional pattern suggesting adaptive or homeostatic mechanisms aimed at maintaining cellular and synaptic balance. Collectively, these findings, accompanied by alterations in behavioral tests, highlight the regional specificity of epigenetic remodeling induced by excessive alcohol exposure during adolescence and offer new insights into the molecular mechanisms underlying increased neurodevelopmental vulnerability during this period.