# Evaluation of the Genetic Contribution of the Neuroinflammatory Response Following Neonatal Alcohol Exposure

> **NIH NIH F31** · UNIVERSITY OF TENNESSEE HEALTH SCI CTR · 2020 · $36,524

## Abstract

Project Summary/Abstract
Although fetal alcohol syndrome was discovered over forty years ago and is entirely preventable, the incidence
of fetal alcohol spectrum disorder (FASD) has not diminished. The type and severity of alcohol-induced
alterations following prenatal alcohol exposure is strongly impacted by genetics. Dr. Kristin Hamre has
demonstrated in BXD recombinant inbred mouse strains with differential vulnerability to FASD that genetics is a
principal factor defining susceptibility to alcohol-induced neuron death in the fetal hippocampus, one of the
regions central to FASD cognitive deficits. However, the mechanisms behind the genetic contribution has not
been identified. Research by Dr. Cynthia Kane has shown that alcohol exposure in the developing brain of
C57BL/6J (B6) mice (a parental strain of the BXD lines) produces neuroinflammatory responses that lead to
neuron death, including production of pro-inflammatory molecules and glial activation in the hippocampus. Her
lab has also found that administration of the peroxisome proliferator-activated receptor-y agonist, pioglitazone,
reduces alcohol-induced neuroinflammatory responses in the developing central nervous system. However, the
role of genetics in neuroinflammatory responses to developmental alcohol exposure has not been determined.
We hypothesize that differential fetal vulnerability to FASD is mediated, at least in part, by genetic differences
leading to variation in the neuroinflammatory response to alcohol in the developing hippocampus. Experiments
outlined in this proposal will: 1) determine whether alcohol-induced neuroinflammatory responses contribute to
the differential genetic vulnerability to alcohol-induced cell loss in the developing hippocampus in Specific Aim 1
and 2) investigate whether administration of the anti-inflammatory drug, pioglitazone, protects highly sensitive
BXD strains from hippocampal cell loss by suppressing alcohol-induced neuroinflammatory responses in
neonatal mice in Specific Aim 2. The effects will be determined by examining expression of mRNA, expression
of protein, percentage of cell loss, and activation of microglia and astrocytes in the hippocampus of neonatal
mice exposed to developmental alcohol. This research will result in a further understanding of 1) the genetic
contributions to the severity of FASD, 2) the genetic influence of alcohol-induced neuroinflammatory responses,
and 3) whether pioglitazone is equally effective at inhibiting alcohol-induced cell loss across animals of differing
genetic backgrounds.

## Key facts

- **NIH application ID:** 9828524
- **Project number:** 5F31AA026498-03
- **Recipient organization:** UNIVERSITY OF TENNESSEE HEALTH SCI CTR
- **Principal Investigator:** Jessica A Baker
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $36,524
- **Award type:** 5
- **Project period:** 2017-12-01 → 2020-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9828524

## Citation

> US National Institutes of Health, RePORTER application 9828524, Evaluation of the Genetic Contribution of the Neuroinflammatory Response Following Neonatal Alcohol Exposure (5F31AA026498-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9828524. Licensed CC0.

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