# Sex and stress: effects on the brain - gut axis

> **NIH NIH R01** · PENNSYLVANIA STATE UNIV HERSHEY MED CTR · 2021 · $344,925

## Abstract

PROJECT SUMMARY
 Women display higher incidence of gastrointestinal disorders, including functional dyspepsia (FD), and
report a higher severity of dyspeptic symptoms compared to men. Although physiological mechanisms that
mediate this sex disparity in gastrointestinal (GI) disorders are not fully understood, it has been suggested that
they may be mediated by circulating estrogen.
 Gastric motility is modulated by neurons of the dorsal motor nucleus of the vagus (DMV) and the activity of
these neurons is regulated by a robust tonic GABAergic input. Estrogen has been shown to increase GABA
expression and release in several regions of the central nervous system (CNS), as well as to modulate
neuronal morphology and synaptic activity.
 Based on our preliminary studies that indicate an estrogen-dependent modulation of vagal output to the
stomach, we will test the following novel hypothesis: “Functional gastrointestinal disorders are increased in
severity and incidence in females due, in part, to an estrogen mediated decrease in vagal outflow to the
stomach”. To investigate this novel hypothesis, we will use a combination of in vitro and in vivo
electrophysiological, behavioral, chemogenetic, and anatomical approaches in a rodent model aimed at
interrogating the role of stress and estrogen on the brain-gut axis.
 The results of the experiments outlined in this proposal will provide a deeper understanding of the cellular
and neural mechanisms by which estrogen influences the etiology of FD, help identify potential targets for
more effective therapeutic interventions directed specifically towards women, and provide novel insights into
changes in GI functions that occur in the perimenopausal period.

## Key facts

- **NIH application ID:** 10146366
- **Project number:** 5R01DK120170-03
- **Recipient organization:** PENNSYLVANIA STATE UNIV HERSHEY MED CTR
- **Principal Investigator:** Kirsteen Nairn Browning
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $344,925
- **Award type:** 5
- **Project period:** 2019-07-01 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10146366

## Citation

> US National Institutes of Health, RePORTER application 10146366, Sex and stress: effects on the brain - gut axis (5R01DK120170-03). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10146366. Licensed CC0.

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