Dulaglutide treatment reverses depression‐like behavior and hippocampal metabolomic homeostasis in mice exposed to chronic mild stress

作者：Man Jin, Shipan Zhang, Boya Huang, Litao Li, Hao Liang, Aihua Ni, Lina Han, Peng Liang, Jing Liu, Haishui Shi, Peiyuan Lv · 发表于：Brain and Behavior · 年份：2024 · DOI：10.1002/brb3.3448 · 被引用次数：14 · 研究领域：Treatment of Major Depression、Tryptophan and brain disorders、Stress Responses and Cortisol

INTRODUCTION: Treatment strategies for depression based on interventions for glucose and lipid metabolism disorders are receiving increasing attention. Investigating the mechanism of their antidepressant effect and exploring new diagnostic and therapeutic biomarkers have attracted increasing attention. Dulaglutide, a long-acting GLP-1 receptor agonist, has been reported to alleviate cognitive deficits and neuronal damage. However, the antidepressant effect of dulaglutide and, especially, the underlying mechanism are still poorly understood. In this study, we aimed to explore the underlying biomarkers of depression and potential modulatory targets of dulaglutide in chronic mild stress (CMS) mice. METHODS: Sixty mice were randomly divided into a control group (CON group), a CMS+Vehicle group (CMS+Veh group), a CMS+0.3 mg/kg dulaglutide group (Low Dula group), and a CMS+0.6 mg/kg dulaglutide group (High Dula group). Numerous behavioral tests, mainly the open field test, forced swimming test, and tail suspension test, were applied to evaluate the potential effect of dulaglutide treatment on anxiety- and depression-like behaviors in mice exposed to chronic stress. Furthermore, a liquid chromatography-tandem mass spectrometry-based metabolomics approach was utilized to investigate the associated mechanisms of dulaglutide treatment. RESULTS: Three weeks of dulaglutide treatment significantly reversed depressive-like but not anxiety-like behaviors in mice exposed to chronic stress fo...