Disturbance of hippocampal H2S generation contributes to CUMS-induced depression-like behavior: involvement in endoplasmic reticulum stress of hippocampus.
The chronic unpredictable mild stress (CUMS) model is a widely used experimental model of depression. Exogenous stress-induced neuronal cell death in the hippocampus is closely associated with the pathogenesis of depression. Excessive and prolonged endoplasmic reticulum (ER) stress triggers cell death. Hydrogen sulfide (H2S), the third endogenous signaling gasotransmitter, plays an important role in brain functions as a neuromodulator and a neuroprotectant. We hypothesized that the disturbance of endogenous H2S generation and ER stress in the hippocampus might be involved in CUMS-induced depression-like behaviors. Thus, the present study focused on whether CUMS disturbs the generation of endogenous H2S and up-regulates ER stress in the hippocampus and whether exogenous H2S prevents CUMS-induced depressive-like behaviors. Results showed that CUMS-treated rats exhibit depression-like behavior and hippocampal ER stress responses including up-regulated levels of glucose-regulated protein 78, CCAAT/enhancer binding protein homologous protein, and cleaved caspase-12 expression, while the endogenous generation of H2S in the hippocampus is suppressed in CUMS-treated rats. Furthermore, exogenous H2S prevents CUMS-induced depression-like behavior. These data indicated that CUMS-induced depression-like behaviors are related to the disturbance of endogenous H2S generation and ER stress in the hippocampus and suggested that endogenous H2S and ER stress are novel treatment targets of depression.
Department of Neurology, Nanhua Affiliated Hospital, University of South China, Hengyang 421001, China Department of Physiology and Institute of Neuroscience, Medical College, University of South China, Hengyang 421001, China Key Laboratory for Cognitive Disorders and Neurodegenerative Diseases, University of South China, Hengyang 421001, China.
Huiying
H
Tan
Department of Neurology, Nanhua Affiliated Hospital, University of South China, Hengyang 421001, China Key Laboratory for Cognitive Disorders and Neurodegenerative Diseases, University of South China, Hengyang 421001, China.
Wei
W
Zou
Department of Physiology and Institute of Neuroscience, Medical College, University of South China, Hengyang 421001, China Key Laboratory for Cognitive Disorders and Neurodegenerative Diseases, University of South China, Hengyang 421001, China.
Jiamei
J
Jiang
Department of Biochemistry, University of South China, Hengyang 421001, China tangxq-usc@qq.com uscty@163.com.
Ying
Y
Tian
Department of Neurology, Nanhua Affiliated Hospital, University of South China, Hengyang 421001, China Department of Physiology and Institute of Neuroscience, Medical College, University of South China, Hengyang 421001, China.
Zhifang
Z
Xiao
Department of Neurology, Nanhua Affiliated Hospital, University of South China, Hengyang 421001, China Department of Physiology and Institute of Neuroscience, Medical College, University of South China, Hengyang 421001, China.
Lili
L
Bi
Department of Neurology, Nanhua Affiliated Hospital, University of South China, Hengyang 421001, China Department of Physiology and Institute of Neuroscience, Medical College, University of South China, Hengyang 421001, China Key Laboratory for Cognitive Disorders and Neurodegenerative Diseases, University of South China, Hengyang 421001, China.
Haiying
H
Zeng
Department of Neurology, Nanhua Affiliated Hospital, University of South China, Hengyang 421001, China Department of Physiology and Institute of Neuroscience, Medical College, University of South China, Hengyang 421001, China Key Laboratory for Cognitive Disorders and Neurodegenerative Diseases, University of South China, Hengyang 421001, China tangxq-usc@qq.com uscty@163.com.
Xiaoqing
X
Tang
D000818:Animals; D015153:Blotting, Western; D053454:Caspase 12 / Q000378:metabolism; D003866:Depressive Disorder / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D059865:Endoplasmic Reticulum Stress / Q000502:physiology; D006360:Heat-Shock Proteins / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism* / Q000503:physiopathology; D006862:Hydrogen Sulfide / Q000378:metabolism*; D008297:Male; D017207:Rats, Sprague-Dawley; D013315:Stress, Psychological / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology; D051742:Transcription Factor CHOP / Q000378:metabolism; D015854:Up-Regulation; D000091342:Endoplasmic Reticulum Chaperone BiP
D053454:Caspase 12; D006360:Heat-Shock Proteins; D006862:Hydrogen Sulfide; D051742:Transcription Factor CHOP; C497251:Ddit3 protein, rat; C051684:GRP78 protein, rat; D000091342:Endoplasmic Reticulum Chaperone BiP; C506443:Casp12 protein, rat
chronic unpredictable mild stress; depression; endoplasmic reticulum stress; hydrogen sulfide