Activation of zona incerta gamma-aminobutyric acid-ergic neurons alleviates depression-like and anxiety-like behaviors induced by chronic restraint stress  

作　　者：Si-Hai Chen Bo Lan Ying-Ying Zhang Guo-Hui Li Yu-Long Qian Ming-Xing Hu Yin-Lin Tian Wei-Dong Zang Jing Cao Guang-Hai Wang Yi-Gang Wang 

机构地区：[1]Department of Psychiatry,Xiaogan Rehabilitation Hospital,Xiaogan 432000,Hubei Province,China [2]School of Basic Medical Sciences,Zhengzhou University,Zhengzhou 450000,Henan Province,China [3]School of Nursing and Health,Zhengzhou University,Zhengzhou 450000,Henan Province,China

出　　处：《World Journal of Psychiatry》2025年第2期209-221,共13页世界精神病学杂志(英文)

基　　金：Supported by the Natural Science Foundation of Xiaogan,China,No.XGKJ2023010036.

摘　　要：BACKGROUND Depression is a prevalent affective disorder,but its pathophysiology remains unclear.Dysfunction in the gamma-aminobutyric acid(GABA)-ergic system may contribute to its onset.Recently,antidepressants(e.g.,brexanolone,zuranolone)targeting the GABA-A receptor were introduced.The zona incerta(ZI),an inhibitory subthalamic region mainly composed of GABAergic neurons,has been implicated in emotional regulation.Deep brain stimulation of the ZI in humans affects anxiety and depression symptoms,while activation of ZI neurons in mice can either worsen or alleviate anxiety.Currently,there is no direct evidence linking GABAergic neurons in the ZI to depression-like behaviors in rodents.AIM To explore the relationship between GABAergic neurons in the ZI and depression-like behaviors in mice.METHODS A chronic restraint stress(CRS)model was utilized to induce depression in mice.Whole-cell patch-clamp recordings assessed the excitability changes of GABAergic neurons in the ZI.Additionally,chemogenetic techniques were employed to modulate ZI GABAergic neurons.The performance of the mice in behavioral tests for depression and anxiety was observed.RESULTS The findings indicated that GABAergic neurons in the ZI were closely associated with depression-like behaviors in mice.Twenty-eight days after the CRS model was established,depression-like and anxiety-like behaviors were observed in the mice.The excitability of GABAergic neurons in the ZI was reduced.Chemogenetic activation of these neurons alleviated CRS-induced depression-like and anxiety-like behaviors.Conversely,inhibition of GABAergic neurons in the ZI led to changes in emotion-related behavioral outcomes in mice.CONCLUSION Activity of GABAergic neurons in the ZI was closely associated with depression-like phenotypes in mice,suggesting that these neurons could be a potential therapeutic target for treating depression.

关 键 词：Zona incerta Gamma-aminobutyric acid-ergic DEPRESSION ANXIETY Animal behavior studies Whole-cell patchclamp 

分 类 号：R749.4[医药卫生—神经病学与精神病学]