Official websites use .gov

A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS

A lock ( 🔒 ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

Need Help

Blunted mechanosensation of the heart and gut as a mediator of pathogenesis conferred by chronic social subjugation

Award Number: R01AT013166
ORGANIZATION: CENTER FOR DRUG EVALUATION AND RESEARCH, NIH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 01/01/2025
PERIOD OF PERFORMANCE END DATE: 11/30/2029

Group Awards By:

View Award Description

Blunted mechanosensation of the heart and gut as a mediator of pathogenesis conferred by chronic social subjugation - Project Summary In the coming decades, cardiometabolic and affective disorders will become an epidemic in the U.S. While wealth and geography contribute to health disparities, emerging evidence indicates that rank within a social hierarchy is a potent predictor of pathogenesis. Consistent with this notion, we’ve determined that mice rendered subordinate in the chronic social defeat stress (CSDS) paradigm become hypertensive, exhibit marked weight gain and increased anxiety-like behavior. Insight on causal mechanisms comes from our prior studies on cardiometabolic interoception. We discovered that neurons within the nodose ganglia that express oxytocin receptors (hereafter referred to as NDGOxtr) serve as mechanoreceptors that relay stretch exerted on the heart and gut to brain circuits orchestrating cardiovascular and gastrointestinal function. Fascinatingly, chemogenetic activation of NDGOxtr imitates the sensation of vascular and gastrointestinal stretch, thereby producing compensatory reductions in blood pressure and food intake. Impaired interoception is implicated in the etiology of cardiometabolic and affective disorders and our preliminary studies suggest that CSDS blunts mechanosensation of the heart and gut. That is, subordinate mice have impaired baroreflex sensitivity, consume large meals, and neurons within the nodose ganglia (NDG) have reduced expression of Piezo2 mRNA (i.e., molecular mechanoreceptor). These observations have led to the overall hypothesis that blunted mechanosensation of the heart and gut by NDGOxtr contributes to the development of cardiometabolic and affective disorders that accompany social adversity. We propose the following three aims to test this hypothesis. Aim 1 uses intravital imaging to investigate the impact of CSDS on NDGOxtr activity in response to mechanical stretch of the vasculature and gut. Aim 2 uses a genetically engineered mouse model to determine whether deleting Piezo2 from NDGOxtr recapitulates and/or exacerbates the effects of CSDS. Aim 3 uses chronic chemogenetics to determine whether stimulating NDGOxtr during CSDS restores cardiometabolic mechanosensation and alleviates the deleterious effects of CSDS. Collectively, our experiments will reveal, at a detailed and mechanistic level, whether 1.) chronic social stress impairs mechanosensation of the heart and gut, 2.) downregulation of Piezo2 within NDGOxtr contributes to the hypertension, hyperphagia, and anxiety-like behavior that comes with chronic social stress, 3.) restoring mechanosensation of the heart and gut by activating specific vagal sensory afferents is a viable therapeutic strategy. By elucidating the mechanisms by which social stress disrupts body-to-brain communication this research has the potential to identify novel therapeutic targets for improving health outcomes in populations experiencing social adversity.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $668,570 )
2026	2026	GEORGIA STATE UNIVERSITY RESEARCH FOUNDATION INC	58 EDGEWOOD AVE NE	ATLANTA	GA	30303	FULTON	USA	Research and Training in Complementary and Integrative Health	000	2	4/29/2026	NON-COMPETING CONTINUATION	$668,570
														Subtotal = $668,570

Issue Date FY: 2025 ( Subtotal = $682,570 )
2025	2025	GEORGIA STATE UNIVERSITY RESEARCH FOUNDATION INC	58 EDGEWOOD AVE NE	ATLANTA	GA	30303	FULTON	USA	Research and Training in Complementary and Integrative Health	000	1	12/30/2024	NEW	$682,570
														Subtotal = $682,570

Grand Total All Awards = $1,351,140

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Blunted mechanosensation of the heart and gut as a mediator of pathogenesis conferred by chronic social subjugation

Award Number: R01AT013166

ORGANIZATION: CENTER FOR DRUG EVALUATION AND RESEARCH, NIH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 01/01/2025

PERIOD OF PERFORMANCE END DATE: 11/30/2029

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer