# Molecular Neurogenetics of the Brainstem Neuronal Source of Cardioprotective Vagal Outflow

> **NIH NIH R01** · THOMAS JEFFERSON UNIVERSITY · 2022 · $571,138

## Abstract

We aim to identify, predict and control the central brainstem neurons that integrate interoceptive inputs to
produce and determine the activity of the vagus nerve in regulating the heart. The level of “vagal outflow” is
strongly associated with the health of the heart. Insufficient vagal outflow contributes to many forms of heart
disease, which appear preventable and, potentially, reversible by increases in cardioprotective vagal outflow.
We aim to study the central neurons within the dorsal motor nucleus of the vagus (DMV) that are an important
source of cardioprotective vagal outflow to the heart, as these are associated with some of the most devastating
diseases of the heart. We will determine the cardioprotective molecular mechanisms in DMV neurons in order to
use this information to intervene and affect those molecular mechanisms in ways that allow control of the vagal
outflow. We will accomplish this through an integrated experimental and computational analysis of the responses
of microRNAs and mRNAs in DMV neurons (e.g., Gorky et al. 2021). We have successfully followed this
approach using microRNA regulation in a parallel project on hypertension (DeCicco et al. 2015; Gorky, DeDicco
et al. in review), and seek to emulate that approach here. We have preliminary DMV data integrating interoceptive
inputs in cardiac ischemia and remote ischemic preconditioning (rIPC) suggesting this approach will be
applicable for vagal cardioprotection in male and female rats. We hypothesize that the vagal outflow that
drives cardioprotection in rIPC derives from an altered molecular activity within the dorsal motor nucleus
of the vagus (DMV), mediated by differential microRNA regulation in DMV neurons. Aim 1 will seek to
renormalize the molecular state of DMV neurons following left anterior descending coronary artery (LAD) ligation
by modulating the microRNA regulatory networks within the DMV. Aim 2 will identify the dynamic trajectory of
rIPC-induced microRNA and gene regulatory networks in DMV to predict rIPC-induced microRNA control points
in DMV that can potentially extend the molecular cardioprotective effect beyond the currently described 24-hour
efficacy window post rIPC. Aim 3 will test the hypothesis that microRNAs regulated in response to rIPC, and
their targets putatively contributing to cardioprotection, are co-regulated in one or more specific subsets of DMV
neurons. We have assembled an interdisciplinary team for this project. Dr. Vadigepalli is a systems biologist with
skills in the analysis of high-dimensional datasets to derive predictions of transcriptional network modules and
of microRNA network regulators. Dr. Schwaber has extensive experience with the integrative circuit
neuroanatomy and neurophysiology of the central mechanisms of vagal cardiac activity. Dr. Brailoiu is an expert
on neuronal processes in the brainstem autonomic nuclei and brings technical expertise on single neuron
isolation and analysis. These studies will take state-o...

## Key facts

- **NIH application ID:** 10522387
- **Project number:** 1R01HL161696-01A1
- **Recipient organization:** THOMAS JEFFERSON UNIVERSITY
- **Principal Investigator:** JAMES SCHWABER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $571,138
- **Award type:** 1
- **Project period:** 2022-07-01 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10522387

## Citation

> US National Institutes of Health, RePORTER application 10522387, Molecular Neurogenetics of the Brainstem Neuronal Source of Cardioprotective Vagal Outflow (1R01HL161696-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10522387. Licensed CC0.

---

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