Abstract
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.
Highlights
Mental tension, emergency incident or other stimulating factors can make the body produce stress reaction
To investigate the ameliorating role of H2S in CRSinduced cognitive impairment in rats, we explored the effect of NaHS on the cognitive function of Chronic restraint stress (CRS) (6 h/d for 28 d)-exposed rats by Y-maze test, Novel object recognition test, and Morris water maze test
We further explored the beneficial effect of H2S on cognitive function of CRS-exposed rats using the Morris water maze (MWM) test
Summary
Emergency incident or other stimulating factors can make the body produce stress reaction. Within the scope of physiological stress response is benefit for the body [1]. When people are in long-term chronic stress situation, their physical and mental health are adversely influenced www.impactjournals.com/oncotarget [2]. Chronic restrain stress (CRS), as a non-invasive stimulation, is able to better simulate a living state of uncontrollable congestion, setbacks in our daily life. It has been reported that CRS can impair hippocampaldependent spatial learning and memory [3], which may be related to stress-caused oxidative damage in the hippocampal neurons and changes in synaptic structure. Further investigation of the potential therapeutic approaches for treatment of CRS-induced hippocampal damage and cognitive impairment will provide new opportunities for improving human health
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