# Astrocyte gene expression and translation in an in vivo FASD mouse model

> **NIH NIH R01** · OREGON HEALTH & SCIENCE UNIVERSITY · 2021 · $326,030

## Abstract

PROJECT SUMMARY
The effects of developmental alcohol exposure on astrocytes remains largely unknown, despite the extensive
and growing evidence of the roles played by these cells both in the developing and adult brain. This gap in
knowledge is due in part to the challenges of studying these cells in vivo. We propose to employ new
technologies allowing the study of astrocytes in vivo to gain mechanistic insights into astrocytic functions
altered by developmental alcohol exposure to advance the pace of our discoveries of the roles played by
astrocytes in Fetal Alcohol Spectrum Disorders (FASD). We propose to use the Aldh1l1-EGFP-Rpl10a mice
that allow for the selective pull down of actively translating RNA from astrocytes by the translating ribosome
affinity purification (TRAP) method and for the isolation of astrocyte-specific nuclei by Fluorescent-Activated
Cell Sorting (FACS). Hence, this system allows to analyze changes in both astrocyte-specific nuclear RNA
expression and astrocyte-specific RNA translation by RNA-seq. We hypothesize that neonatal alcohol
exposure induces extensive changes in the translation of genes involved in several astrocyte-mediated
processes in vivo and on molecular stuctures mainly contributed by astrocytes, such as the extracellular matrix
(ECM) that modulate some of these processes. We also hypothesize that changes in translation are in part
driven by changes in transcription and in part independent from transcription. Additionally, the proposed
studies will assess astrocyte heterogeneity in their response to developmental alcohol exposure across
developmental stages, sexes, and brain regions. The cell type-specificity of the proposed studies will help to
disentangle astrocyte function and dysfunction in FASD from contributions of other cell types. We are
particularly interested in alterations involving the ECM as we have reported that several proteins of the ECM
play important roles in neuronal development and are dysregulated by ethanol. We expect the results of our
proposed Aims to be very impactful to the FASD field. We will study the prefrontal cortex (PFC) and
hippocampus (HPC) of developing (PD7) and adult (PD90) female and male Aldh1l1-EGFP-Rpl10a mice. Aim
1: To identify changes in the astrocyte nuclear transcriptome induced by neonatal ethanol exposure by FACS
sorting of astrocyte nuclei followed by RNA-seq and pathway analysis. Aim 2: To identify changes in the
astrocyte translatome induced by neonatal ethanol exposure by TRAP-RNA-seq and integrate these findings
with transcriptome data. Aim 3: To explore the dysregulation of the astrocyte ECM network that underlies some
of the developmental effects of ethanol by TRAP-qPCR, Fluorescence In Situ Hybridization (FISH)-RNAscope,
Western blot, and immunohistochemistry to validate at both mRNA and protein levels ethanol-induced changes
in ECM proteins. The proposed studies address NIH/NIAA priorities as they will provide mechanistic insights
into astrocyte functi...

## Key facts

- **NIH application ID:** 10285484
- **Project number:** 1R01AA029486-01
- **Recipient organization:** OREGON HEALTH & SCIENCE UNIVERSITY
- **Principal Investigator:** Marina Guizzetti
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $326,030
- **Award type:** 1
- **Project period:** 2021-09-01 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10285484

## Citation

> US National Institutes of Health, RePORTER application 10285484, Astrocyte gene expression and translation in an in vivo FASD mouse model (1R01AA029486-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10285484. Licensed CC0.

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