RNA m6A Modification Changes in Postmortem Nucleus Accumbens of Subjects with Alcohol Use Disorder: A Pilot Study.

Abstract

Background: The nucleus accumbens (NAc) is a key brain structure mediating the rewarding effect of alcohol and drug abuse. Chronic alcohol consumption may alter RNA methylome (or epitranscriptome) in the NAc, leading to altered gene expression and thus behavioral neuroadaptation to alcohol. Methods: This pilot study profiled the epitranscriptomes of mRNAs, long noncoding RNAs (lncRNAs), and microRNAs (miRNAs) in postmortem NAc of three male Caucasian subjects with alcohol use disorder (AUD) and three matched male Caucasian control subjects using Arraystar’s m6A-mRNA&lncRNA Epitranscriptomic Microarray assay. Differentially methylated (DM) RNAs and the function of DM RNAs were analyzed by biostatistics and bioinformatics programs. Results: 26 mRNAs were hypermethylated and three mRNAs were hypomethylated in the NAc of AUD subjects (≥2-fold changes and p ≤ 0.05). Most of these 29 DM mRNAs are involved in immune-related pathways (e.g., IL-17 signaling). Moreover, four lncRNAs were hypermethylated and one lncRNA was hypomethylated in the NAc of AUD subjects (≥2-fold changes and p ≤ 0.05). Additionally, three miRNAs were hypermethylated in the NAc of AUD subjects (≥2-fold changes and p ≤ 0.05). Conclusions: This study revealed RNA methylomic changes in the NAc of AUD subjects, suggesting that chronic alcohol consumption may lead to AUD through epitranscriptomic RNA modifications. Our findings need to be replicated in a larger sample.