# Effects of adolescent ethanol exposure on astrocyte-neuronal crosstalk

> **NIH NIH R21** · MARSHALL UNIVERSITY · 2024 · $175,750

## Abstract

ABSTRACT
Adolescent binge drinking promotes enduring cognitive deficits and higher incidence of alcohol use disorder in
adulthood. Studies using a rat model of adolescent binge drinking (EtOH) demonstrate long-term deficits in
hippocampal neuronal structure, function, and behavior; however, the underlying mechanisms are not well
understood. Coincident with changes in CA1 hippocampal neuronal circuit function, adolescent EtOH exposure
results in astrocyte reactivity and 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 remote memory, and contribute to working
memory deficits following drug exposure. Current data demonstrates that EtOH-induced persistence of
immature dendritic spines (i.e. sites of excitatory synaptic input) is spatiotemporally linked with PAP-synaptic
decoupling. Based on preliminary data the researchers predict that disruption of PAP proximity to synapses
compromises neuron-to-astrocyte signaling and the ability of astrocytes to regulate synaptic homeostasis.
Therefore, the overall objective of this application is to elucidate how EtOH-induced disruption of PAP-synaptic
coupling and neuron-astrocyte crosstalk contributes to long-term changes in synaptic function. Achieving this
objective will allow the researchers to reach their 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 adolescent EtOH exposure. The central hypothesis is that repeated
adolescent EtOH exposure triggers PAP-synaptic decoupling and lasting changes in astrocyte-neuronal
crosstalk. The rationale behind the project is that understanding the novel mediators that drive EtOH-induced
maladaptive astrocyte-neuronal crosstalk will contribute key insight into the mechanisms underlying synaptic
dysfunction following adolescent EtOH exposure. The proposed research is significant since successful
completion will result in the identification of non-neuronal processes critical for the prevention and reversal of
neuronal circuit dysfunction following adolescent ethanol exposure. An interdisciplinary team of investigators
and consultants with expertise in the field of adolescent alcohol, astrocytes, and electrophysiology will conduct
this innovative project.

## Key facts

- **NIH application ID:** 10809011
- **Project number:** 5R21AA030086-02
- **Recipient organization:** MARSHALL UNIVERSITY
- **Principal Investigator:** Mary-Louise Risher
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $175,750
- **Award type:** 5
- **Project period:** 2023-03-15 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10809011

## Citation

> US National Institutes of Health, RePORTER application 10809011, Effects of adolescent ethanol exposure on astrocyte-neuronal crosstalk (5R21AA030086-02). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10809011. Licensed CC0.

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