Tang Yi-Yun, Wang Ai-Ping, Wei Hai-Jun, Li Man-Hong, Zou Wei, Li Xiang, Wang Chun-Yan, Zhang Ping, Tang Xiao-Qing
Institute of Neuroscience, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, Medical College, University of South China, Hengyang, 421001, Hunan, PR China; Department of Physiology, Medical College, University of South China, Hengyang, 421001, Hunan, PR China.
Institute of Neuroscience, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, Medical College, University of South China, Hengyang, 421001, Hunan, PR China; Department of Anatomy, Medical College, University of South China, Hengyang, 421001, Hunan, PR China.
Behav Brain Res. 2018 Apr 16;342:35-42. doi: 10.1016/j.bbr.2017.12.040. Epub 2018 Jan 4.
Homocysteine (Hcy) causes cognitive deficits and hippocampal endoplasmic reticulum (ER) stress. Our previous study has confirmed that Hydrogen sulfide (HS) attenuates Hcy-induced cognitive dysfunction and hippocampal ER stress. Silent information regulator 1 (Sirt-1) is indispensable in the formation of learning and memory. Therefore, the aim of this study was to explore the role of Sirt-1 in the protective effect of HS against Hcy-induced cognitive dysfunction. We found that NaHS (a donor of HS) markedly up-regulated the expression of Sirt-1 in the hippocampus of Hcy-exposed rats. Sirtinol, a specific inhibitor of Sirt-1, reversed the improving role of NaHS in the cognitive function of Hcy-exposed rats, as evidenced by that sirtinol increased the escape latency and the swim distance in the acquisition trial of morris water maze (MWM) test, decreased the times crossed through and the time spent in the target quadrant in the probe trail of MWM test, and reduced the discrimination index in the novel object recognition test (NORT) in the rats cotreated with NaHS and Hcy. We also found that sirtinol reversed the protection of NaHS against Hcy-induced hippocampal ER-stress, as evidenced by up-regulating the expressions of GRP78, CHOP, and cleaved caspase-12 in the hippocampus of rats cotreated with NaHS and Hcy. These results suggested the contribution of upregulation of hippocampal Sirt-1 to the improving role of HS in the cognitive function of Hcy-exposed rats, which involves suppression of hippocampal ER stress. Our finding provides a new insight into the mechanism underlying the inhibitory role of HS in Hcy-induced cognitive dysfunction.
同型半胱氨酸（Hcy）会导致认知缺陷和海马内质网（ER）应激。我们之前的研究已证实，硫化氢（HS）可减轻Hcy诱导的认知功能障碍和海马ER应激。沉默信息调节因子1（Sirt-1）在学习和记忆的形成中不可或缺。因此，本研究旨在探讨Sirt-1在HS对Hcy诱导的认知功能障碍的保护作用中的作用。我们发现，NaHS（一种HS供体）显著上调了Hcy暴露大鼠海马中Sirt-1的表达。Sirtinol是Sirt-1的特异性抑制剂，它逆转了NaHS对Hcy暴露大鼠认知功能的改善作用，这表现为Sirtinol增加了莫里斯水迷宫（MWM）试验获取试验中的逃避潜伏期和游泳距离，减少了MWM试验探测试验中穿过目标象限的次数和在目标象限停留的时间，并降低了与NaHS和Hcy共同处理的大鼠在新物体识别试验（NORT）中的辨别指数。我们还发现，Sirtinol逆转了NaHS对Hcy诱导的海马ER应激的保护作用，这表现为上调了与NaHS和Hcy共同处理的大鼠海马中GRP78、CHOP和裂解的caspase-12的表达。这些结果表明，海马Sirt-1的上调有助于HS对Hcy暴露大鼠认知功能的改善作用，这涉及抑制海马ER应激。我们的发现为HS对Hcy诱导的认知功能障碍的抑制作用机制提供了新的见解。
