# Long-term effects of binge drinking on astrocyte-synaptic interactions

> **NIH VA I01** · HUNTINGTON VETERANS AFFAIRS MED CTR · 2024 · —

## Abstract

Operation Enduring Freedom in Afghanistan and Operation Iraqi Freedom (OEF/OIF) studies report that
combat veterans are at increased risk for binge drinking and the development of alcohol use disorder (AUD).
38% of Army active duty members surveyed returning from OEF/OIF deployments between 2008 and 2011
reported binge drinking. Furthermore, veterans between the ages of 20 and 25 are 2.21 times more likely to
binge drink and 2.24 times more likely to have an AUD than their peers aged 46 years or older, outlining the
prevalence of alcohol abuse in the young veteran population. Importantly, more than 50% of males surveyed
reported hazardous binge drinking even prior to deployment. Despite repeated binge drinking being associated
with acute and long-term cognitive impairment and increased likelihood of developing AUD, the underlying
mechanisms are not well understood.
 Studies using a rat model of binge drinking called chronic intermittent ethanol exposure (CIE) demonstrate
long-term deficits in hippocampal neuronal structure, function, and behavior. We have shown that, coincident
with changes in CA1 hippocampal neuronal circuit function, binge ethanol (EtOH) exposure results in chronic
dysregulation of astrocyte-secreted signaling factors known to be involved in synaptic remodeling. Astrocytes
tightly regulate synaptic activity and ion homeostasis through their perisynaptic astrocyte processes (PAPs),
allowing for bi-directional communication through various contact-mediated and secreted signaling factors that
modulate synaptic transmission. In addition, the behavioral relevance of astrocyte/synaptic communication is
beginning to emerge through exciting new advances showing astrocytes to be involved in behavioral resiliency,
fear learning, and contributing to working memory deficits following drug exposure.
 Our current data demonstrate that EtOH-induced persistence of immature dendritic spines (i.e. sites of
excitatory synaptic input) is spatiotemporally linked with PAP-synaptic decoupling. We predict that disruption of
PAP proximity to synapses compromises the ability of astrocytes to regulate synaptic homeostasis. Therefore,
the overall objective of this application is to elucidate how EtOH-induced disruption of astrocyte function and
PAP-synaptic coupling contributes to long-term changes in synaptic networks. Achieving this objective will
allow us to reach our long-term goal, which is to identify the cellular and molecular mechanisms that may
inform novel treatments for the prevention and reversal of synaptic dysfunction and the emergence of AUD
after repeated binge EtOH exposure. Our central hypothesis is that repeated binge EtOH exposure triggers
aberrant astrocyte signaling and disruption of PAP-synaptic proximity that drive lasting deficits in synaptic
structure and homeostasis. The rationale behind this project is that understanding how disruption of astrocyte
function and PAP-synaptic communication occur will contribute key insight into t...

## Key facts

- **NIH application ID:** 10980501
- **Project number:** 5I01BX005403-04
- **Recipient organization:** HUNTINGTON VETERANS AFFAIRS MED CTR
- **Principal Investigator:** Mary-Louise Risher
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2024
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2021-07-01 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10980501

## Citation

> US National Institutes of Health, RePORTER application 10980501, Long-term effects of binge drinking on astrocyte-synaptic interactions (5I01BX005403-04). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10980501. Licensed CC0.

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