Hydrogen Sulfide Inhibits Chronic Unpredictable Mild Stress-Induced Depressive-Like Behavior by Upregulation of Sirt-1: Involvement in Suppression of Hippocampal Endoplasmic Reticulum Stress.
Hydrogen Sulfide Inhibits Chronic Unpredictable Mild Stress-Induced Depressive-Like Behavior by Upregulation of Sirt-1: Involvement in Suppression of Hippocampal Endoplasmic Reticulum Stress.
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硫化氢通过上调 Sirt-1 抑制慢性不可预测的轻度应激诱发的抑郁样行为：参与抑制海马内质网应激。
DOI：
10.1093/ijnp/pyx030
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发表时间：
2017-11-01
期刊：
影响因子：
--
通讯作者：
Tang XQ
中科院分区：
文献类型：
--
作者：
Liu SY;Li D;Zeng HY;Kan LY;Zou W;Zhang P;Gu HF;Tang XQ
硫化氢（H2S）是一种具有广泛生理功能的重要信号分子。之前，我们证实应激性抑郁伴随海马中H2S生成的紊乱。本研究旨在探讨H2S对慢性不可预测的轻度应激诱导的抑郁样行为的抑制作用及其机制。我们建立慢性不可预测轻度应激大鼠模型来模拟抑郁症。采用空地试验、强迫游泳试验和悬尾试验评估抑郁样行为。western blot检测Sirt-1及3种内质网应激相关标记蛋白（GRP-78、CHOP、cleaved caspase-12）的表达。我们发现慢性不可预测轻度应激暴露大鼠表现出抑郁样行为反应，包括在强迫游泳测试和悬尾测试中不动时间显著增加，在强迫游泳测试中攀爬时间和游泳时间显著减少。同时，慢性不可预测的轻度应激暴露大鼠显示海马内质网应激水平升高，Sirt-1水平降低。然而，NaHS （H2S供体）不仅可以缓解慢性不可预测轻度应激诱导的抑郁样行为和海马内质网应激，还可以增加慢性不可预测轻度应激暴露大鼠海马Sirt-1的表达。此外，Sirtinol， Sirt-1的抑制剂，逆转H2S对慢性不可预测的轻度应激诱导的抑郁样行为和海马内质网应激的保护作用。这些结果表明H2S具有抗抑郁潜能，其潜在机制可能与通过上调海马Sirt-1抑制海马内质网应激有关。这些发现表明H2S是一种新的治疗抑郁症的靶点。
Hydrogen sulfide (H2S) is a crucial signaling molecule with a wide range of physiological functions. Previously, we confirmed that stress-induced depression is accompanied with disturbance of H2S generation in hippocampus. The present work attempted to investigate the inhibitory effect of H2S on chronic unpredictable mild stress-induced depressive-like behaviors and the underlying mechanism. We established the rat model of chronic unpredictable mild stress to simulate depression. Open field test, forced swim test, and tail suspension test were used to assess depressive-like behaviors. The expression of Sirt-1 and three marked proteins related to endoplasmic reticulum stress (GRP-78, CHOP, and cleaved caspase-12) were detected by western blot. We found that chronic unpredictable mild stress-exposed rats exhibit depression-like behavior responses, including significantly increased immobility time in the forced swim test and tail suspension test, and decreased climbing time and swimming time in the forced swim test. In parallel, chronic unpredictable mild stress-exposed rats showed elevated levels of hippocampal endoplasmic reticulum stress and reduced levels of Sirt-1. However, NaHS (a donor of H2S) not only alleviated chronic unpredictable mild stress-induced depressive-like behaviors and hippocampal endoplasmic reticulum stress, but it also increased the expression of hippocampal Sirt-1 in chronic unpredictable mild stress-exposed rats. Furthermore, Sirtinol, an inhibitor of Sirt-1, reversed the protective effects of H2S against chronic unpredictable mild stress-induced depression-like behaviors and hippocampal endoplasmic reticulum stress. These results demonstrated that H2S has an antidepressant potential, and the underlying mechanism is involved in the inhibition of hippocampal endoplasmic reticulum stress by upregulation of Sirt-1 in hippocampus. These findings identify H2S as a novel therapeutic target for depression.
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影响因子：
16.2
作者：
Herskovits AZ;Guarente L
通讯作者：
Guarente L
DOI：
10.3988/jcn.2009.5.3.120
发表时间：
2009-09
期刊：
Journal of clinical neurology (Seoul, Korea)
影响因子：
--
作者：
Han SH
通讯作者：
Han SH
影响因子：
3.7
作者：
Ferrari AJ;Norman RE;Freedman G;Baxter AJ;Pirkis JE;Harris MG;Page A;Carnahan E;Degenhardt L;Vos T;Whiteford HA
通讯作者：
Whiteford HA
影响因子：
11.4
作者：
Kim, Dohoon;Nguyen, Minh Dang;Tsai, Li-Huei
通讯作者：
Tsai, Li-Huei
影响因子：
2
作者：
Ishisaka, Mitsue;Kakefuda, Kenichi;Hara, Hideaki
通讯作者：
Hara, Hideaki