# 3/8 NADIA U01 Adolescent Alcohol, Epigenetics and Behavioral Changes in Adulthood

> **NIH NIH U01** · UNIVERSITY OF ILLINOIS AT CHICAGO · 2020 · $399,750

## Abstract

ABSTRACT
Several clinical and preclinical studies suggest that adolescent binge drinking is one of the major risk factors for
the development of psychiatric disorders, including anxiety and alcohol use disorder (AUD) later in life.
Adolescence represents an important stage of brain development, and epigenetic mechanisms are known to
orchestrate developmental maturation of the brain from adolescence to adulthood. This research component of
Neurobiology of Adolescent Drinking in Adulthood (NADIA) consortium will examine how epigenetic
modifications induced by adolescent intermittent ethanol (AIE) at the genome-wide level lead to an aberrant
gene network pathway regulating various synaptic mechanisms in the amygdala that are responsible for anxiety-
like and alcohol drinking behavior in adulthood. This component will identify closed and open domains of the
epigenome after AIE in adult amygdala using Assay for Transposase-Accessible Chromatin-sequencing (ATAC-
seq), and the corresponding regulation of the transcriptome by merging this dataset with existing RNA-seq data.
The overarching hypothesis of this proposal is that AIE will produce differential gene expression due to
altered status of the epigenome in adult amygdala. The dynamic changes in epigenetic targets
(HATs/EZH2/G9a/LSD1/DNMT3b) will induce changes in the transcriptome that regulate synaptic
mechanisms in the amygdala after AIE in adulthood, ultimately regulating anxiety-like and alcohol-
drinking behaviors. Specific Aim 1 will examine a) the status of chromatin accessibility and loci of genomic
epigenetic marks using ATAC-seq in the adult amygdala of rats (male & female) after AIE. The emerging data
set will be merged with existing RNA-seq data to identify epigenetically regulated transcriptomic changes, and
b) To validate expression and epigenetic enrichments of new genes in the amygdala after AIE and use them for
functional studies. Specific Aim 2 will examine the effects of neuronal epigenomic editing in the CeA using
CRISPR/dCas9-p300, CRISPR/dCas9-KRAB, CRISPR/dCas9-Lsd1 (histone acetylation/methylation), or
CRISPR/dCAS9-Tet1 (DNA methylation mechanism) on AIE-induced changes in gene expression and on
anxiety-like and alcohol drinking behaviors in adult male and female rats. Specific Aim 3 will examine whether
treatment with G9a inhibitor (UNC0642) will normalize epigenetic, gene expression, and dendritic spine changes
in the amygdala and attenuate AIE-induced anxiety-like and alcohol drinking behaviors in adult male and female
rats. Finally, Specific Aim 4 will translate epigenetic dynamics and expression of novel genes that will be
identified from RNA-seq and ATAC-seq in the AIE rat amygdala to post-mortem amygdala of human alcoholics
with early age onset and correlate them to drinking data (daily or weekly ethanol intake). The proposed studies
will provide new information about epigenetic regulation of the whole transcriptome in the amygdala after AIE,
leading to identification ...

## Key facts

- **NIH application ID:** 10074051
- **Project number:** 2U01AA019971-11
- **Recipient organization:** UNIVERSITY OF ILLINOIS AT CHICAGO
- **Principal Investigator:** SUBHASH C. PANDEY
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $399,750
- **Award type:** 2
- **Project period:** 2010-09-01 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10074051

## Citation

> US National Institutes of Health, RePORTER application 10074051, 3/8 NADIA U01 Adolescent Alcohol, Epigenetics and Behavioral Changes in Adulthood (2U01AA019971-11). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10074051. Licensed CC0.

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