Tan Huiying, Zou Wei, Jiang Jiamei, Tian Ying, Xiao Zhifang, Bi Lili, Zeng Haiying, Tang Xiaoqing
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.
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.
Acta Biochim Biophys Sin (Shanghai). 2015 Apr;47(4):285-91. doi: 10.1093/abbs/gmv009. Epub 2015 Mar 2.
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.
慢性不可预测性轻度应激（CUMS）模型是一种广泛应用的抑郁症实验模型。外源性应激诱导的海马神经元细胞死亡与抑郁症的发病机制密切相关。过度且持久的内质网（ER）应激会触发细胞死亡。硫化氢（H2S）作为第三种内源性信号气体递质，作为神经调节剂和神经保护剂在脑功能中发挥重要作用。我们假设海马中内源性H2S生成和ER应激的紊乱可能与CUMS诱导的抑郁样行为有关。因此，本研究聚焦于CUMS是否会扰乱海马中内源性H2S的生成并上调ER应激，以及外源性H2S是否能预防CUMS诱导的抑郁样行为。结果显示，经CUMS处理的大鼠表现出抑郁样行为以及海马ER应激反应，包括葡萄糖调节蛋白78、CCAAT/增强子结合蛋白同源蛋白水平上调以及半胱天冬酶-12裂解表达增加，而经CUMS处理的大鼠海马中内源性H₂S生成受到抑制。此外，外源性H2S可预防CUMS诱导的抑郁样行为。这些数据表明，CUMS诱导的抑郁样行为与海马中内源性H2S生成和ER应激的紊乱有关，并提示内源性H2S和ER应激是抑郁症的新治疗靶点。
