Alcohol Effects on Human Gene Expression

MicroRNAs (miRNAs) are small noncoding genes implicated in gene expression regulation and protein production. In the context of alcohol use disorder (AUD), excessive alcohol consumption can lead to lasting changes in brain function, affecting mRNA regulation and synaptic plasticity. Notably, preclinical studies show alcohol-induced decreases in miRNAs 494 and 130a in the amygdala are related to anxiolytic-like effects of alcohol. Our study aimed to extend these findings to humans by investigating expression of miRNA-130a and miRNA-494 in peripheral monocytes of moderate-heavy drinkers. Healthy participants consumed 0 and 80mg% alcohol during separate test sessions. Self-reported mood and drug effects were measured before and at repeated times after drinking, and blood samples were collected 2h after drinking for analysis of miR130a, mir490, and BDNF. In comparison to placebo, 80mg% alcohol increased expression of mir130a (p<0.05) and mir494 (p=0.08), and decreased BDNF levels (p<0.01). Alcohol effects on expression of miRNA 130a and 494 were positively correlated(p<0.05) and mir494 expression was negatively correlated with BDNF levels. Alcohol effects on mir494 and BDNF were also related to the self-reported subjective effects of alcohol during sessions; individuals with the greatest increases in mir494 and decreases in BDNF reported the greatest sedative effects and negative subjective responses (dysphoria, confusion) to alcohol. Our study translates preclinical findings of alcohol epigenetic regulation mechanisms to humans. Notably, we found relationships between alcohol effects on gene expression and subjective mood. Discrepancies in alcohol effects on gene expression between preclinical data and the present study may be due to the exposure history of participants; moderate-heavy alcohol drinkers vs. naïve rats. Our study's clinical relevance lies in its potential to identify molecular biomarkers of AUD and inform personalized treatment approaches. Future studies will expand on the dynamics of microRNA and BDNF expression and effects on cognitive functioning.

Presented at Undergraduate Reserach Forum 2023