# Astrocytes, alcohol, and the extracellular matrix

> **NIH NIH P60** · OREGON HEALTH & SCIENCE UNIVERSITY · 2021 · $122,962

## Abstract

PROJECT SUMMARY – P002
Several genome-wide studies, including studies from the previous funding period of the PARC, identified the
extracellular matrix (ECM) and astrocytes as being involved in both the risk for and the effects of ethanol
drinking. Cells in the brain parenchyma are separated by the extracellular space, accounting for approximately
20% of the total volume of the mature rodent brain and containing a highly organized ECM that forms an
insoluble network around cells. The brain interstitial ECM significantly contributes to the molecular signals
regulating neuronal plasticity. Recent research has shown that astrocytes are major producers of the brain
interstitial ECM as well as ECM proteases, which are involved in the remodeling of the ECM. ECM proteins are
post-translationally modified by glycosylation. Proteoglycans are major components of the brain ECM and
consist of a core protein covalently bound to glycosaminoglycans (GAGs) formed by repeating disaccharides,
modified by sulfation. Hyaluronic acid (HA), also a major component of the ECM, is a non-sulfated GAG and is
not covalently bound to proteins. GAGs are involved in the modulation of neuronal plasticity. The overall goal
of this proposal is to identify differential expression of astrocyte-specific genes (with a major emphasis on
genes involved in the formation and remodeling of the ECM) and differential levels of ECM GAGs associated
with ethanol drinking in two brain regions involved in addiction: the medial prefrontal cortex (mPFC; including
the prelimbic and infralimbic cortex) and the nucleus accumbens (NAc). We plan to reach this overarching goal
by pursuing the following two specific aims: 1) Definition of the astrocyte translatome in the mPFC and NAc of
naïve and ethanol-drinking Aldh1l1-EGFP-Rpl10a mice; validation of differential translation and expression by
qPCR and by RNA scope, respectively, in Aldh1l1-EGFP-Rpl10a mice; determination of the expression of
selected ECM-related genes in ethanol naïve high ethanol preference (HP) and low ethanol preference (LP)
mice, and in ethanol-drinking HP mice by RNAscope. We will use the translating ribosome affinity purification
(TRAP) technology in Aldh1l1-EGFP-Rpl10a mice that express a modified ribosomal protein Rpl10a with an
eGFP tag (EGFP-Rpl10a) only in cells expressing the astrocytic marker Aldh1l1. Selected differentially
translated RNAs for ECM-related proteins will be confirmed by qPCR and their differential expression and sub-
regional localization will be determined by RNAscope. Differential expression of selected ECM-related genes
will also be determined in ethanol naïve HP vs. LP mice to investigate genes involved in the risk of ethanol
drinking and in drinking and naïve HP mice to investigate the effects of ethanol drinking in this selected line by
RNAscope. 2) Determination of chondroitin sulfate (CS)-, heparan sulfate (HS)-, and HA-GAG disaccharide
levels in the mPFC and NAc of ethanol naïve and ethanol-drinkin...

## Key facts

- **NIH application ID:** 10056067
- **Project number:** 2P60AA010760-26
- **Recipient organization:** OREGON HEALTH & SCIENCE UNIVERSITY
- **Principal Investigator:** Marina Guizzetti
- **Activity code:** P60 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $122,962
- **Award type:** 2
- **Project period:** 1996-12-01 → 2025-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10056067

## Citation

> US National Institutes of Health, RePORTER application 10056067, Astrocytes, alcohol, and the extracellular matrix (2P60AA010760-26). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10056067. Licensed CC0.

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