Researchers Erica Periandri and Gabor Egervari from Washington University in St. Louis reported on Mar. 30 that alcohol exposure changes gene expression and regulatory mechanisms in the brains of male mice. The study, published in eNeuro, examined how both brief and repeated alcohol exposure influences epigenetics—the processes that control gene function—in various brain regions.
The findings are important because they reveal that the effects of alcohol on the brain are not uniform but depend on both the amount of exposure and the specific area of the brain affected. This could have implications for understanding how alcohol use leads to changes associated with disorders like addiction.
Egervari said, "We recently uncovered that metabolites [from the body's breakdown] of alcohol directly regulate genes in the hippocampus following a one-time exposure to alcohol. This is a previously unknown and surprisingly direct way in which alcohol impacts the brain, and it was not known to what extent these mechanisms occur in other brain regions. Now, we wanted to see whether these new mechanisms are active in other brain areas and following repeated exposures to alcohol." According to their research, after brief exposure, some assessed areas showed altered gene regulation due to alcohol metabolites; after longer exposures, all assessed areas were affected. However, overall results varied by region.
The researchers found that many epigenetic and gene expression programs were more strongly influenced by short-term rather than long-term exposure. They also noted that molecular changes in a part of the brain called the ventral hippocampus—which is involved with emotion and motivation—were especially sensitive to how many times mice were exposed to alcohol.
According to Periandri and Egervari's team, their work demonstrates that "how much exposure a mouse has to alcohol determines which genes and gene regulatory mechanisms are affected in some brain regions, especially in the ventral hippocampus." They caution that sex differences were not studied but say their identified markers may help inform future treatments for alcohol use disorder.
