Dulaglutide treatment reverses depression-like behavior and hippocampal metabolomic homeostasis in mice exposed to chronic mild stress
© 2024 The Authors. Brain and Behavior published by Wiley Periodicals LLC..
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 for 4 weeks. The results from the metabolomics analysis showed that a total of 20 differentially expressed metabolites were identified between the CON and CMS+Veh groups, and 46 metabolites were selected between the CMS+Veh and High Dula groups in the hippocampus of the mice. Comprehensive analysis indicated that lipid metabolism, amino acid metabolism, energy metabolism, and tryptophan metabolism were disrupted in model mice that experienced depression and underwent dulaglutide therapy.
CONCLUSION: The antidepressant effects of dulaglutide in a CMS depression model were confirmed. We identified 64 different metabolites and four major pathways associated with metabolic pathophysiological processes. These primary data provide a new perspective for understanding the antidepressant-like effects of dulaglutide and may facilitate the use of dulaglutide as a potential therapeutic strategy for depression.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:14 |
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| Enthalten in: |
Brain and behavior - 14(2024), 3 vom: 13. März, Seite e3448 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Jin, Man [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 07.03.2024 Date Revised 08.03.2024 published: Print Citation Status MEDLINE |
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| doi: |
10.1002/brb3.3448 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM369341651 |
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| 245 | 1 | 0 | |a Dulaglutide treatment reverses depression-like behavior and hippocampal metabolomic homeostasis in mice exposed to chronic mild stress |
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| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2024 The Authors. Brain and Behavior published by Wiley Periodicals LLC. | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a RESULTS: Three weeks of dulaglutide treatment significantly reversed depressive-like but not anxiety-like behaviors in mice exposed to chronic stress for 4 weeks. The results from the metabolomics analysis showed that a total of 20 differentially expressed metabolites were identified between the CON and CMS+Veh groups, and 46 metabolites were selected between the CMS+Veh and High Dula groups in the hippocampus of the mice. Comprehensive analysis indicated that lipid metabolism, amino acid metabolism, energy metabolism, and tryptophan metabolism were disrupted in model mice that experienced depression and underwent dulaglutide therapy | ||
| 520 | |a CONCLUSION: The antidepressant effects of dulaglutide in a CMS depression model were confirmed. We identified 64 different metabolites and four major pathways associated with metabolic pathophysiological processes. These primary data provide a new perspective for understanding the antidepressant-like effects of dulaglutide and may facilitate the use of dulaglutide as a potential therapeutic strategy for depression | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a depression | |
| 650 | 4 | |a dulaglutide | |
| 650 | 4 | |a liquid chromatography-tandem mass spectrometry | |
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| 650 | 7 | |a WTT295HSY5 |2 NLM | |
| 650 | 7 | |a Antidepressive Agents |2 NLM | |
| 650 | 7 | |a Biomarkers |2 NLM | |
| 650 | 7 | |a Glucagon-Like Peptides |2 NLM | |
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| 650 | 7 | |a Immunoglobulin Fc Fragments |2 NLM | |
| 650 | 7 | |a Recombinant Fusion Proteins |2 NLM | |
| 700 | 1 | |a Zhang, Shipan |e verfasserin |4 aut | |
| 700 | 1 | |a Huang, Boya |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Litao |e verfasserin |4 aut | |
| 700 | 1 | |a Liang, Hao |e verfasserin |4 aut | |
| 700 | 1 | |a Ni, Aihua |e verfasserin |4 aut | |
| 700 | 1 | |a Han, Lina |e verfasserin |4 aut | |
| 700 | 1 | |a Liang, Peng |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Jing |e verfasserin |4 aut | |
| 700 | 1 | |a Shi, Haishui |e verfasserin |4 aut | |
| 700 | 1 | |a Lv, Peiyuan |e verfasserin |4 aut | |
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