# Chronic alcohol effects on the biogenesis, distribution, and RNA content of astrocytic exosomes

> **NIH NIH R21** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2024 · $187,031

## Abstract

PROJECT SUMMARY/ABSTRACT
 Neuronal dysfunction underlies the general pathophysiological mechanisms related to heavy alcohol use
and development of alcohol use disorder (AUD). Homeostatic glia-neuron communications underlie the
development and functional maintenance of the central nervous system (CNS). Alcohol-induced neuropathology
has been demonstrated to involve dysregulation of glia-neuron interactions, but the exact molecular and cellular
mechanisms remain elusive. Evidence suggests involvement of extracellular vesicles, including exosomes, in
CNS communication and the pathogenesis of CNS diseases. Recent studies point to the exosome as a potential
mediator of astrocyte-neuron interactions. It has been shown that exosomes released from astrocytes are
internalized by neurons and also that neuronal activity-dependent exosome secretion from astrocytes may
modulate the efficacy of synaptic transmission and the preservation of axonal health. These suggest an important
contribution of astrocyte-neuron communication by exosomes to neuronal integrity. Moreover, the utility of brain-
derived plasma exosomes as a biomarker for neuropathology has been demonstrated. Thus, it has been shown
that genetic information associated with brain tumor or brain injury is detectable in plasma/serum microvesicles
of patients, suggesting that brain-derived exosomes may serve as cargo for diagnostic biomarkers. Astrocytic
exosomes may also play significant roles in the pathophysiology of AUD, but it is unknown if heavy alcohol
exposure affects the biogenesis of astrocytic exosomes, their trafficking and distribution, and further biological
functions. This R21 exploratory grant application is designed to address our hypothesis that chronic alcohol
affects the biogenesis and distribution of astrocyte-derived exosomes and their molecular components thereby
affecting astrocyte-neuron communication. We propose two Specific Aims to achieve our immediate goals: (1)
develop an in vivo model of astrocyte-derived exosome tracking with which to profile the astrocyte-derived
exosomal RNAs, and (2) determine the effect of chronic intermittent ethanol (CIE) vapor exposure on the
biogenesis, distribution, and RNA signatures of astrocyte-derived exosomes. By achieving these aims, we will
be able to determine the potential roles of astrocyte exosomes in transducing the effects of chronic alcohol
exposure onto neuronal cells. We will also gain insight into the potential utility of brain-origin exosomes and their
contents as biomarkers of alcohol dependence-related abnormalities. This reporter model may then be used to
study the mechanisms of astrocyte involvement in various CNS homeostatic functions and numerous other
pathological conditions.

## Key facts

- **NIH application ID:** 10988592
- **Project number:** 1R21AA031366-01A1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** YONG KIM
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $187,031
- **Award type:** 1
- **Project period:** 2024-09-01 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10988592

## Citation

> US National Institutes of Health, RePORTER application 10988592, Chronic alcohol effects on the biogenesis, distribution, and RNA content of astrocytic exosomes (1R21AA031366-01A1). Retrieved via AI Analytics 2026-06-23 from https://api.ai-analytics.org/grant/nih/10988592. Licensed CC0.

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