# Alcohol, Exercise & the Female Brain

> **NIH NIH R01** · UNIVERSITY OF HOUSTON · 2021 · $344,250

## Abstract

Project Summary
 Alcohol use disorder (AUD) is a significant public health problem in the United States. Binge pattern
consumption, the most common form of AUD, damages corticolimbic brain regions essential for cognition and
behavioral control, including the hippocampus. Compared to men, women disproportionately experience
alcohol-related health problems, including organ damage, and a growing body of research indicates that they
are also more likely than men to suffer alcohol-induced brain damage. The apparent vulnerability of the female
brain to alcohol necessitates a more thorough understanding of underlying mechanisms, to inform the
development of effective treatment strategies. Our preliminary data from a rat model show sex-dependent
effects of binge alcohol on the hippocampus and hippocampal-dependent cognition, with females significantly
more negatively affected, and our proposed experiments will develop this model. The traditional suspects when
investigating sex differences are gonadal hormones, either due to their permanent, organizational effects or
their transient, activational (circulating) effects. Because circulating ovarian hormones are protective against
other forms of brain injury, such as stroke, the vulnerability of the female brain to alcohol damage presents a
conundrum. To resolve it, our proposed experiments will test the novel hypothesis that early organizational (but
not circulating) sex hormone effects are responsible for the selective vulnerability of the female brain to binge
alcohol exposure. Finally, although the female hippocampus may be selectively vulnerable to binge alcohol, we
have also found that it can be repaired by exercise. We will use this model of exercise-driven repair to probe
underlying mechanisms and address the novel question of whether the repaired hippocampus functions like
the never-damaged hippocampus. Using a clinically-relevant rodent model, our three specific aims will 1)
establish the selective vulnerability of the female brain to binge alcohol; 2) determine the contribution of
organizational and/or circulating sex hormone effects and 3) pinpoint mechanisms and efficacy of exercise-
driven restoration. Our findings will elucidate the mechanisms underlying female brain susceptibility to alcohol
damage and inform the development of novel interventions to enhance brain repair.

## Key facts

- **NIH application ID:** 10147617
- **Project number:** 5R01AA025380-04
- **Recipient organization:** UNIVERSITY OF HOUSTON
- **Principal Investigator:** J Leigh Leasure
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $344,250
- **Award type:** 5
- **Project period:** 2018-08-01 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10147617

## Citation

> US National Institutes of Health, RePORTER application 10147617, Alcohol, Exercise & the Female Brain (5R01AA025380-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10147617. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*