# Supplement: Adolescent intermittent ethanol induction of neuroimmune signaling disrupts the mature phenotype of surviving hippocampal neuroprogenitors

> **NIH NIH K99** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2024 · $48,070

## Abstract

PROJECT SUMMARY
Unlike adult alcohol exposure, the cellular and behavioral effects of adolescent binge drinking do not recover following
periods of abstinence, suggesting that alcohol exposure across adolescence has the potential to permanently disrupt the
brain’s developmental trajectory. However, while prior research has focused on the underlying mechanisms driving this
loss and restoration of newborn hippocampal neurons, no research has investigated how adolescent intermittent
ethanol (AIE) impacts the ability of surviving hippocampal neuroprogenitor cells (NPCs) to appropriately integrate into
adult hippocampal circuitry. In order to test the impact of adolescent alcohol on network integration of developing
neurons, we will use a reporter mouse line (DCX-CreERT2/tdtomato) which was developed to specifically tag and then
fate-map NPCs across their lifespan. This technique will allow us to track how alcohol impacts the ability of adolescent
maturing neurons to effectively integrate into mature dentate circuitry. We will test whether AIE impairs proper
formation of dendritic arborization in adolescent-maturing NPCs (AIM 1/K99). We will then test whether adolescent
alcohol further impairs the electrophysiological properties of these NPCs in adulthood (AIM 2/K99). As it remains unclear
whether maturational changes in neurons mediate loss of behavioral flexibility, we will test whether adolescent ethanol
impairs neuronal activation in response to behavioral flexibility tasks (AIM 3/K99). However, due to the additional
burdens of childcare following the birth of my firstborn son, Leonardo Preston (4/18/2023), I am requesting this
supplement to support hiring a research technician in order to expedite the immunohistochemical components of the
parent grant. The aims of this project will remain unchanged with this supplement request, and the technical training
aspects of this grant (ex vivo electrophysiology, Aim 2) will continued to be performed by myself. Collectively, these
experiments will provide critical insight into the impact of adolescent alcohol on the resulting phenotypic fate and circuit
regulation of surviving NPCs in both sexes.

## Key facts

- **NIH application ID:** 11014162
- **Project number:** 3K99AA030089-02S1
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Victoria Alice Macht
- **Activity code:** K99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $48,070
- **Award type:** 3
- **Project period:** 2022-09-01 → 2024-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11014162

## Citation

> US National Institutes of Health, RePORTER application 11014162, Supplement: Adolescent intermittent ethanol induction of neuroimmune signaling disrupts the mature phenotype of surviving hippocampal neuroprogenitors (3K99AA030089-02S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/11014162. Licensed CC0.

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