# Effects of chronic alcohol consumption on the synaptic translatome

> **NIH NIH R03** · TEXAS TECH UNIVERSITY HEALTH SCIS CENTER · 2021 · $79,155

## Abstract

Project Summary/Abstract
Repeated alcohol (ethanol) exposure results in cellular adaptations that are thought to be critical for the
transition from low/moderate drinking to excessive alcohol consumption, which is a prerequisite for the
development of Alcohol Use Disorder (AUD). Local protein synthesis (translation) in dendrites and axons
plays a central role in synaptic plasticity and neuroadaptations to environmental challenges including
exposure to drugs. Acute and chronic alcohol changes RNA abundance in synaptic terminals, suggesting a
change in local protein synthesis, but we do not know which specific mRNAs undergo active translation at
the synapse (the synaptic translatome) in response to alcohol. Actively translated synaptic mRNAs are
mechanistically linked to neuronal functions and provide primary mechanistic candidates for alcohol-induced
neuroadaptations. Here, we propose to use a combination of synaptoneurosome preparations and
polysome profiling followed by RNA sequencing (RNA-Seq) to determine changes in the synaptic
translatome after chronic alcohol drinking in mice. Synaptoneurosomes have been widely used to study
molecular functions at the synapse in health and disease and polysome profiling is the gold standard for
studying cellular translatomes. Because the synaptoneurosome/polysome profiling combination has not
been used in alcohol studies, our initial goal is to develop/optimize the existing methodology for alcohol
research. Alcohol-preferring C57BL/6J mice will be exposed to alcohol for several weeks using a 2-bottle
choice chronic intermittent alcohol drinking paradigm that is used as a model of escalating alcohol
consumption. The prefrontal cortex, a critical brain region implicated in AUD, will be dissected and
subjected to the synaptoneurosome/polysome profiling followed by RNA-Seq. We hypothesize that chronic
alcohol intake will affect the synaptic translatome and change local protein synthesis in the prefrontal cortex,
which may contribute to neuroadaptations underlying high alcohol drinking. These initial experiments will
identify alcohol-sensitive actively translated synaptic mRNAs (genes) that may eventually be targeted to
reduce alcohol intake via manipulation of synaptic functions. The long-term goal of this research is to
determine the role of local protein synthesis in brain mechanisms underlying AUD traits. This knowledge
may be used to develop new therapies for the prevention and treatment of AUD.

## Key facts

- **NIH application ID:** 10148599
- **Project number:** 5R03AA028370-02
- **Recipient organization:** TEXAS TECH UNIVERSITY HEALTH SCIS CENTER
- **Principal Investigator:** Igor Ponomarev
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $79,155
- **Award type:** 5
- **Project period:** 2020-05-01 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10148599

## Citation

> US National Institutes of Health, RePORTER application 10148599, Effects of chronic alcohol consumption on the synaptic translatome (5R03AA028370-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10148599. Licensed CC0.

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