Hydrogen sulfide attenuates chronic restrain stress-induced cognitive impairment by upreglulation of Sirt1 in hippocampus.
Hydrogen sulfide attenuates chronic restrain stress-induced cognitive impairment by upreglulation of Sirt1 in hippocampus.
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DOI：
10.18632/oncotarget.22237
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发表时间：
2017-11-21
期刊：
影响因子：
--
通讯作者：
Tang XQ
中科院分区：
文献类型：
--
作者：
Li XN;Chen L;Luo B;Li X;Wang CY;Zou W;Zhang P;You Y;Tang XQ
慢性束缚应激（CRS）对认知功能有不利影响。硫化氢（H2S）作为一种神经调质，调节学习和记忆。海马是学习和记忆的关键结构。沉默信号调节因子1（silence signal regulating factor 1，Sirt 1）在认知功能的调节中起着重要作用。因此，我们目前的工作是调查是否H2S改善CRS诱导的海马损伤和认知障碍，并进一步探讨其潜在的机制是否是通过上调Sirt 1。本研究通过行为学实验[Y-迷宫实验、新物体识别（NOR）实验、Morris水迷宫（MWM）实验]发现，硫氢化钠（NaHS）可阻断CRS诱导的大鼠认知障碍。NaHS抑制CRS诱导的海马氧化应激，表现为降低MDA水平以及增加GSH含量和SOD活性。NaHS拯救了CRS产生的ER应激，如通过下调CPR 78、CHOP和裂解的caspase-12所证明的。NaHS减少CRS引起的细胞凋亡，如TUNEL阳性细胞和Bax表达的数量减少以及Bcl-2表达的增加所证明的。NaHS上调CRS暴露大鼠海马Sirt 1的表达。此外，Sirtinol抑制Sirt 1逆转NaHS对CRS引起的认知功能障碍和氧化应激，ER应激以及海马细胞凋亡的保护作用。总之，这些结果表明，H2S通过上调海马Sirt 1改善CRS诱导的海马损伤和认知障碍。
Chronic restraint stress (CRS) has detrimental effects on cognitive function. Hydrogen sulfide (H2S), as a neuromodulator, regulates learning and memory. Hippocampus is a key structure in learning and memory. Sirt1 (silence signal regulating factor 1) plays an important role in modulating cognitive function. Therefore, our present work was to investigate whether H2S meliorates CRS-induced damage in hippocampus and impairment in cognition, and further to explore whether the underlying mechanism is via upreglulating Sirt1. In our present work, the behavior experiments [Y-maze test, Novel object recognition (NOR) test, Morris water maze (MWM) test] showed that sodium hydrosulfide (NaHS, a donor of H2S) blocked CRS-induced cognitive impairments in rats. NaHS inhibited CRS-induced hippocampal oxidative stress as evidenced by decrease in MDA level as well as increases in GSH content and SOD activity. NaHS rescued CRS-generated ER stress as evidenced by downregulations of CPR78, CHOP, and cleaved caspase-12. NaHS reduced CRS-exerted apoptosis as evidenced by decreases in the number of TUNEL-positive cells and Bax expression as well as increase in Bcl-2 expression. NaHS upregulated the expression of Sirt1 in the hippocampus of CRS-exposed rats. Furthermore, inhibited Sirt1 by Sirtinol reversed the protective effects of NaHS against CRS-produced cognitive dysfunction and oxidative stress, ER stress as well as apoptosis in hippocampus. Together, these results suggest that H2S meliorates CRS-induced hippocampal damage and cognitive impairment by upregulation of hippocampal Sirt1.
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胱硫醚-β-合酶衍生的硫化氢是大鼠杏仁核长期增强和提示恐惧记忆所必需的。
影响因子：
3.6
作者：
Chen, Hai-Bo;Wu, Wen-Ning;Yang, Yuan-Jian
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DOI：
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发表时间：
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期刊：
Science's STKE : signal transduction knowledge environment
影响因子：
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作者：
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影响因子：
10.5
作者：
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DOI：
10.1523/jneurosci.0027-10.2010
发表时间：
2010-07-21
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
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通讯作者：
Longo VD