# Distinct roles of POMC and AgRP neurons in chronic stress-induced depressive behaviors

> **NIH NIH R56** · AUGUSTA UNIVERSITY · 2020 · $183,292

## Abstract

PROJECT SUMMARY
Depression is a chronic and debilitating mental illness. Anhedonia, one of the two core symptoms
of major depression, is particularly difficult to treat. Individuals can experience one or more types
of anhedonia, defined as a loss of interest or a loss of pleasure. However, the neural circuits and
molecular substrates underlying anhedonia and other key depressive symptoms remain poorly
understood. The arcuate nucleus (ARC) of the hypothalamus contains two distinct neuronal
populations expressing proopiomelanocortin (POMC) and agouti-related protein (AgRP) that are
well known for their roles in homeostatic and hedonic control of feeding. We demonstrated that
chronic unpredictable stress causes different types of anhedonia and behavioral despair and
induces opposite changes in spontaneous firing rate of POMC and AgRP neurons. We
hypothesize that POMC and AgRP neurons play distinct roles in chronic stress-induced
depressive behaviors. The specific aims of this project are designed to determine 1) how chronic
unpredictable stress regulates POMC and AgRP neuronal activity; 2) whether SIRT1 in POMC
and AgRP neurons functions as a molecular mediator of chronic stress-induced depressive
behaviors and neuronal dysfunction; and 3) whether selective activation or inhibition of POMC
and AgRP neurons causes or reverses depressive behaviors.

## Key facts

- **NIH application ID:** 9882506
- **Project number:** 5R56MH119456-02
- **Recipient organization:** AUGUSTA UNIVERSITY
- **Principal Investigator:** Xin-Yun Lu
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $183,292
- **Award type:** 5
- **Project period:** 2019-04-01 → 2022-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9882506

## Citation

> US National Institutes of Health, RePORTER application 9882506, Distinct roles of POMC and AgRP neurons in chronic stress-induced depressive behaviors (5R56MH119456-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9882506. Licensed CC0.

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