# Alcohol Effects on the Proteome and Transcriptome of Fetal Neural Stem Cell-Derived Extracellular Vesicles: Mechanism for Alcohol Teratogenesis

> **NIH NIH F31** · TEXAS A&M UNIVERSITY HEALTH SCIENCE CTR · 2020 · $34,025

## Abstract

Project Summary
Prenatal alcohol exposure (PAE) can result in decreased neurogenic capacity of neural stem cells (NSCs),
which, during the early-to-mid gestation period, give rise to most neurons of the adult brain. This loss of
neurogenic capacity explains, in part, neurobehavioral and brain growth deficits associated with Fetal Alcohol
Spectrum Disorders (FASD). However, the mechanisms that mediate the persistent effects of episodic PAE on
fetal NSCs are unknown. We and others have recently identified a novel class of sub-200 nanometer-sized
extracellular vesicles (EVs) secreted by NSCs, as a means for intercellular transfer of biomolecules including
proteins and nucleic acids. I hypothesize that EVs constitute endocrine-like organelles that propagate the effects
of ethanol throughout the stem cell microenvironment in time and space.
My preliminary and published data support the hypotheses that ethanol (i) alters the sequestration of proteins
into EVs released by fetal NSCs, in a dose-dependent manner, and, by interfering with protein expression in
EVs, (ii) results in loss of stem cell renewal and diminished neurogenesis. Using mass spectrometric and
transcriptomic tools and cell and molecular biological analyses of EV function in a murine model, planned and
completed studies address the following specific aims: Aim 1 seeks to identify and validate the effects of alcohol
exposure on proteins and RNAs in EVs and associated NSCs. My studies show that EVs from parent NSCs
exposed to moderate doses of ethanol (Mod-EtoHEVs) exhibit a significant increase in proteins of the Nonsense-
Mediated Decay (NMD), whereas EVs obtained following NSC exposure to higher levels of ethanol (Hi-EtoHEVs)
overexpress mitochondrial proteins that constitute a Danger-Associated Molecular Pattern (mito-DAMP) signal.
These data will be validated and compared to the ethanol-affected intracellular proteome of parent NSCs. Aim
2 will evaluate the mediating role of Mod-EtoHEV-derived NMD on NSC proliferation, differentiation, and death,
under basal and ethanol-exposure conditions. Our working hypothesis is that Mod-EtoHEVs transfer NMD
components to recipient cells to confer compensatory neuroprotection. Aim 3 will evaluate the mediating role of
Hi-EtoHEV-derived mito-DAMP on NSC proliferation, differentiation, and death. Our working hypothesis is that the
secretion of a ‘danger’ signal in response to high levels of ethanol exposure triggers a pro-inflammatory cytokine
response in recipient NSCs, resulting in impaired neurogenesis.
My studies are expected to uncover novel intercellular communication pathways that mediate the effects of PAE
on early neural maturation. This training plan will equip me with technical and research methodology skills and
develop specific competency with data analytic and statistical approaches for proteome and transcriptome
assessment. The plan’s focus on dissecting and disrupting the connection between PAE and FASD integrates
well with my career...

## Key facts

- **NIH application ID:** 10156239
- **Project number:** 1F31AA028446-01A1
- **Recipient organization:** TEXAS A&M UNIVERSITY HEALTH SCIENCE CTR
- **Principal Investigator:** Dae Chung
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $34,025
- **Award type:** 1
- **Project period:** 2020-09-01 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10156239

## Citation

> US National Institutes of Health, RePORTER application 10156239, Alcohol Effects on the Proteome and Transcriptome of Fetal Neural Stem Cell-Derived Extracellular Vesicles: Mechanism for Alcohol Teratogenesis (1F31AA028446-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10156239. Licensed CC0.

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