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©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Psychiatry. Feb 19, 2025; 15(2): 101807
Published online Feb 19, 2025. doi: 10.5498/wjp.v15.i2.101807
Published online Feb 19, 2025. doi: 10.5498/wjp.v15.i2.101807
Activation of zona incerta gamma-aminobutyric acid-ergic neurons alleviates depression-like and anxiety-like behaviors induced by chronic restraint stress
Si-Hai Chen, Bo Lan, Guo-Hui Li, Yu-Long Qian, Ming-Xing Hu, Yin-Lin Tian, Guang-Hai Wang, Yi-Gang Wang, Department of Psychiatry, Xiaogan Rehabilitation Hospital, Xiaogan 432000, Hubei Province, China
Si-Hai Chen, Ying-Ying Zhang, Wei-Dong Zang, Jing Cao, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450000, Henan Province, China
Jing Cao, School of Nursing and Health, Zhengzhou University, Zhengzhou 450000, Henan Province, China
Co-first authors: Si-Hai Chen and Bo Lan.
Co-corresponding authors: Guang-Hai Wang and Yi-Gang Wang.
Author contributions: Wang YG, Wang GH, Cao J, and Chen SH conceptualized the study; Chen SH, Lan B, and Zhang YY designed the methodology; Chen SH and Lan B performed the formal analysis of the data; Li GH, Qian YL, Hu MX, and Tian YL performed the validation of the data; Hu MX performed the investigation; Tian YL provided necessary resources; Wang YG performed the data curation; Chen SH prepared the original draft of the manuscript; Wang YG, Wang GH, and Chen SH reviewed and edited the subsequent versions of the manuscript; Chen SH generated the data visualizations; Zang WD and Cao J provided overall supervision; Wang YG, Wang GH, and Cao J provided overall project administration; All authors read and approved the published version of the manuscript. Chen SH and Lan B were designated as co-first authors due to the importance of their collaboration in the overall generation of the manuscript and performance of the study. Wang GH and Wang YG were designated as co-corresponding authors to reflect their equal duties in the overall management of the study.
Supported by the Natural Science Foundation of Xiaogan, China, No. XGKJ2023010036.
Institutional animal care and use committee statement: The use of the animals was approved by the Animal Care and Use Committee of Zhengzhou University. All animal experiments conformed to the internationally accepted principles for the care and use of laboratory animals.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: Raw data are available upon reasonable request at wygang1004@163.com.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Yi-Gang Wang, Associate Chief Physician, Department of Psychiatry, Xiaogan Rehabilitation Hospital, No. 99 Huanchuan Road, Xiaonan District, Xiaogan 432000, Hubei Province, China. wygang1004@163.com
Received: September 27, 2024
Revised: November 25, 2024
Accepted: December 18, 2024
Published online: February 19, 2025
Processing time: 109 Days and 4.7 Hours
Revised: November 25, 2024
Accepted: December 18, 2024
Published online: February 19, 2025
Processing time: 109 Days and 4.7 Hours
Core Tip
Core Tip: Gamma-aminobutyric acid (GABA)-ergic dysfunction may play a role in the onset of depression. Case reports have indicated that deep brain stimulation of the zona incerta (ZI), which is abundant in GABAergic neurons, can modify depressive and anxiety symptoms. However, direct evidence linking ZI GABAergic neurons to depression-related behaviors in rodents is limited. This study demonstrated chronic resistant stress induced depression-like and anxiety-like behaviors in mice and reduced neuronal excitability. Chemogenetic activation alleviated these symptoms, whereas inhibition altered the behavior of normal mice. These findings suggested that ZI GABAergic neurons may serve as potential therapeutic targets for depression.