# Neuromolecular consequences of adolescent binge drinking

> **NIH NIH R01** · LOYOLA UNIVERSITY CHICAGO · 2023 · $375,489

## Abstract

According to the CDC, “binge drinking is the most common, costly and deadliest pattern of alcohol use”. The
adolescent period is marked by formative changes in neuronal structure and function; therefore, alcohol abuse
during this vulnerable time period can result in permanent neurological damage and adult behavioral deficits.
Our research and others from the past decade have described numerous long-lasting and transgenerational
neurobiological consequences that can result from adolescent binge drinking. However, the molecular
mechanism of how EtOH exerts immediate effects on the cellular microenvironment to perpetuate these long-
term effects have not been fully ascertained. EtOH can readily enter cells and immediately activate the cellular
stress response, which can then impact transcriptional and translational processes as well as post-translational
modifications of existing proteins. We predict these immediate EtOH-induced effects on the cellular
environment prime the cell to drive the long-term changes we and others have observed. This proposal is a
competitive renewal and this next phase of the project will mechanistically define how EtOH induced
modifications to the glucocorticoid receptor (GR), which then impacts long-term GR function. GRs sit at a
pivotal interface to direct long-lasting changes in the cellular transcriptome and proteome, as they are the core
molecular mediators of the systemic and cellular stress response. Our published and preliminary data suggest
that these key mediators of cellular homeostasis are vulnerable to perturbations by EtOH, especially during
adolescence. Aim 1 will determine by absolute quantification the amount of phosphorylated GR (pGR) in the
brain using our in vivo model of adolescent repeated binge EtOH exposure and mechanistically link GR
phosphorylation with long-term HPA axis dysfunction. In addition, we will investigate novel post-translational
modifications to GR that are induced by adolescent binge EtOH exposure. Aim 2 will determine the suite of
proteins interacting with pGR at specific target genes and identify how EtOH disrupts these GR-protein
association. Aim 3 will investigate how EtOH induces alternative GR mRNA splicing and the mechanisms
regulating splicing. Understanding these fundamental molecular changes could uncover novel therapeutic
targets that may prevent dysregulated cellular signaling leading to behavioral abnormalities later in life.

## Key facts

- **NIH application ID:** 10706623
- **Project number:** 5R01AA021517-07
- **Recipient organization:** LOYOLA UNIVERSITY CHICAGO
- **Principal Investigator:** Toni R. Pak
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $375,489
- **Award type:** 5
- **Project period:** 2013-09-01 → 2027-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10706623

## Citation

> US National Institutes of Health, RePORTER application 10706623, Neuromolecular consequences of adolescent binge drinking (5R01AA021517-07). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10706623. Licensed CC0.

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