Role of silent information regulator 1 in the protective effect of hydrogen sulfide on homocysteine-induced cognitive dysfunction: Involving reduction of hippocampal ER stress

被引：22
|
作者：
Tang, Yi-Yun [1 ,2 ]
Wang, Ai-Ping [1 ,3 ]
Wei, Hai-Jun [1 ,2 ]
Li, Man-Hong [1 ,4 ]
Zou, Wei [1 ,4 ]
Li, Xiang [1 ,5 ]
Wang, Chun-Yan [1 ,6 ]
Zhang, Ping [1 ,4 ]
Tang, Xiao-Qing [1 ,2 ,4 ]
机构：
[1] Univ South China, Inst Neurosci, Med Coll, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Hengyang 421001, Hunan, Peoples R China
[2] Univ South China, Dept Physiol, Med Coll, 28 W Changsheng Rd, Hengyang 421001, Hunan, Peoples R China
[3] Univ South China, Dept Anat, Med Coll, Hengyang 421001, Hunan, Peoples R China
[4] Univ South China, Nanhua Affiliated Hosp, Dept Neurol, 336 E Dongfeng Rd, Hengyang 421001, Hunan, Peoples R China
[5] Univ South China, Dept Anaesthesiol, Affiliated Hosp 1, Hengyang 421001, Hunan, Peoples R China
[6] Univ South China, Dept Pathophysiol, Med Coll, Hengyang 421001, Hunan, Peoples R China
来源：
BEHAVIOURAL BRAIN RESEARCH | 2018年 / 342卷
关键词：
Hydrogen sulfide; Homocysteine; Silent mating type information regulation 2 homolog 1; Endoplasmic reticulum stress; Cognitive dysfunction; ENDOPLASMIC-RETICULUM STRESS; SPATIAL MEMORY IMPAIRMENT; ALZHEIMERS-DISEASE; PLASMA HOMOCYSTEINE; UP-REGULATION; RISK-FACTOR; SIRT1; HYPERHOMOCYSTEINEMIA; PATHWAY; SYSTEM;
D O I：
10.1016/j.bbr.2017.12.040
中图分类号：
B84 [心理学]; C [社会科学总论]; Q98 [人类学];
学科分类号：
03 ; 0303 ; 030303 ; 04 ; 0402 ;
摘要：
Homocysteine (Hcy) causes cognitive deficits and hippocampal endoplasmic reticulum (ER) stress. Our previous study has confirmed that Hydrogen sulfide (H2S) 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 H2S against Hcy-induced cognitive dysfunction. We found that NaHS (a donor of H2S) 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 H2S 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 H2S in Hcy-induced cognitive dysfunction.
引用
收藏
页码：35 / 42
页数：8
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