# Identifying Brain Epitranscriptomic Changes Associated with Alcohol Use Disorder

> **NIH NIH R01** · BOSTON UNIVERSITY MEDICAL CAMPUS · 2022 · $587,928

## Abstract

PROJECT SUMMARY/ABSTRACT
Alcohol use disorder (AUD) affects about 4.2% (or 14.1 million) of American adults each year and causes
substantial morbidity and mortality. While genetic variation can influence an individual's vulnerability to AUD,
chronic alcohol consumption can also lead to alcohol tolerance and dependence, but the underlying mechanism
is unclear. There is evidence that that chronic alcohol use alters DNA methylation of specific genes, leading to
gene expression changes and possibly an increased risk of AUD. RNA methylation is a common post-
transcriptional modification, and it responds rapidly to a variety of stimuli and translates stimulatory signals into
cellular activity. We hypothesize that alcohol use alters an individual's RNA methylome (or epitranscriptome),
resulting in altered expression of genes involved in AUD-related pathways. The objective of this research is to
explore messenger RNA (mRNA) methylomic changes in the brain of AUD subjects and analyze the effect of
mRNA methylation on mRNA expression and neuronal activity, thus providing evidence for a new gene
expression regulatory mechanism of AUD. To achieve this goal, we propose three specific aims. First, we will
profile mRNA methylomic and transcriptomic changes in eight regions (amygdala, caudate, cerebellum,
hippocampus, nucleus accumbens, prefrontal cortex, putamen, and ventral tegmental area) of postmortem
brains of AUD subjects. Second, we will use chronic intermittent ethanol (CIE)-exposed mice as models to verify
AUD-associated brain mRNA methylation and expression changes as well as the correlation of ethanol
exposure-induced mRNA methylation and expression changes with the escalation of ethanol self-administration
in mice. Third, we will employ a novel epitranscriptome editing approach to investigate the effect of AUD-
associated mRNA methylation changes on mRNA expression and neuronal activity. We expect to (1) observe
AUD-associated mRNA methylation and expression changes in specific (or across) brain regions; (2) verify AUD-
associated mRNA methylation and expression changes by mouse modeling; and (3) confirm the functional role
of AUD-associated mRNA methylation in regulating mRNA expression and neuronal activity. Our study design
is innovative. AUD-associated mRNA methylation changes will be examined at single-base resolution. An
integrative study approach (human postmortem brain studies, mouse modeling, and epitranscriptome editing)
will be employed. The proposed research will provide evidence about the influence of brain epitranscriptomic
changes on AUD risk. Given that mRNA methylation is dynamic and reversible, mRNAs with differential
methylation in the brain of AUD subjects could be potential targets for AUD treatment by pharmacologically
altering mRNA methylation status.

## Key facts

- **NIH application ID:** 10343021
- **Project number:** 1R01AA029758-01
- **Recipient organization:** BOSTON UNIVERSITY MEDICAL CAMPUS
- **Principal Investigator:** Huiping Zhang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $587,928
- **Award type:** 1
- **Project period:** 2022-03-01 → 2026-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10343021

## Citation

> US National Institutes of Health, RePORTER application 10343021, Identifying Brain Epitranscriptomic Changes Associated with Alcohol Use Disorder (1R01AA029758-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10343021. Licensed CC0.

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