Alcohol impacts gene expression differently across brain regions

Erica Periandri and Gabor Egervari, from Washington University in St. Louis, led a study to explore how alcohol exposure in male mice influences gene expression and mechanisms that regulate gene function-or epigenetics. Says Egervari, "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." 

As presented in their eNeuro paper, the researchers discovered that alcohol metabolites altered gene regulatory mechanisms in some assessed brain areas after brief exposure and in all assessed brain areas after lengthy exposure to alcohol. But largely, the overall epigenetic and gene expression outcomes varied by brain region. Notably, many epigenetic and gene expression programs were more powerfully altered by short-term alcohol exposure. Molecular changes in a brain area called the ventral hippocampus, which supports emotion and motivated behaviors, were particularly sensitive to the number of times mice were exposed to alcohol. 

According to the researchers, this work shows 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. While noting the caveat that they did not explore sex differences, the researchers emphasize that the markers they identified may be informative for alcohol use disorder treatment development.