Disturbance of hippocampal H2S generation contributes to CUMS-induced depression-like behavior: involvement in endoplasmic reticulum stress of hippocampus.
Disturbance of hippocampal H2S generation contributes to CUMS-induced depression-like behavior: involvement in endoplasmic reticulum stress of hippocampus.
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海马 H2S 生成紊乱会导致 CUMS 诱导的抑郁样行为：参与海马内质网应激。
DOI：
10.1093/abbs/gmv009
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发表时间：
2015-04
期刊：
影响因子：
--
通讯作者：
Tang Xiaoqing（唐小卿）
中科院分区：
文献类型：
--
作者：
Tan Huiying;Zou Wei;Jiang Jiamei;Tian Ying;Xiao Zhifang;Bi Lili;Zeng Haiying;Tang Xiaoqing（唐小卿）
慢性不可预测轻度应激（CUMS）模型是一种应用广泛的抑郁症实验模型。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。过度和长时间的内质网应激会引发细胞死亡。硫化氢（H2S）是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。我们假设内源性H2S生成的紊乱和海马内质网应激可能参与了cums诱导的抑郁样行为。因此，本研究的重点是CUMS是否会干扰内源性H2S的产生，上调海马内质网应激，以及外源性H2S是否会阻止CUMS诱导的抑郁样行为。结果显示，cums处理大鼠表现出抑郁样行为和海马内质网应激反应，包括葡萄糖调节蛋白78、CCAAT/增强子结合蛋白同源蛋白和cleaved caspase-12表达水平上调，而cums处理大鼠海马内源性H2S生成受到抑制。此外，外源性H2S可以阻止coms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内源性H2S生成和内质网应激紊乱有关，提示内源性H2S和内质网应激是抑郁症治疗的新靶点。
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.
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DOI：
10.1523/jneurosci.16-03-01066.1996
发表时间：
1996-02
期刊：
--
影响因子：
--
作者：
K. Abe;H. Kimura
通讯作者：
K. Abe;H. Kimura
影响因子：
21.3
作者：
Tabas, Ira;Ron, David
通讯作者：
Ron, David
影响因子：
3.1
作者：
Xiao-Qing Tang;Yuan-Yuan Zhuang-Yuan;Ping Zhang;Heng-Rong Fang;Cheng-fang Zhou;Hong-Feng Gu;Hui Zhang;
通讯作者：
Xiao-Qing Tang;Yuan-Yuan Zhuang-Yuan;Ping Zhang;Heng-Rong Fang;Cheng-fang Zhou;Hong-Feng Gu;Hui Zhang;
DOI：
10.1523/jneurosci.22-09-03386.2002
发表时间：
2002-05
期刊：
The Journal of Neuroscience
影响因子：
--
作者：
K. Eto;Miki Ogasawara;K. Umemura;Y. Nagai;H. Kimura
通讯作者：
K. Eto;Miki Ogasawara;K. Umemura;Y. Nagai;H. Kimura
影响因子：
2
作者：
Ishisaka, Mitsue;Kakefuda, Kenichi;Hara, Hideaki
通讯作者：
Hara, Hideaki