Inhibited Endogenous H2S Generation and Excessive Autophagy in Hippocampus Contribute to Sleep Deprivation-Induced Cognitive Impairment.

San-Qiao Yang,Li Jiang,Hai-Jun Wei,Ping Zhang,Wei Zou,Yu-Rong Xie,Xiao-Qing Tang,Fang Lan,Ming Xie,Chun-Yan Wang

doi:10.3389/fpsyg.2019.00053

Abstract

Background and Aim: Sleep deprivation (SD) causes deficit of cognition, but the mechanisms remain to be fully established. Hydrogen sulfide (H2S) plays an important role in the formation of cognition, while excessive and prolonged autophagy in hippocampus triggers cognitive disorder. In this work, we proposed that disturbances in hippocampal endogenous H2S generation and autophagy might be involved in SD-induced cognitive impairment.Methods: After treatment of adult male wistar rats with 72-h SD, the Y-maze test, object location test (OLT), novel object recognition test (NORT) and the Morris water maze (MWM) test were performed to determine the cognitive function. The autophagosome formation was observed with electron microscope. Generation of endogenous H2S in the hippocampus of rats was detected using unisense H2S microsensor method. The expressions of cystathionine-β-synthase (CBS), 3-mercaptopyruvate sulfurtransferase (3-MST), beclin-1, light chain LC3 II/LC3 I, and p62 in the hippocampus were assessed by western blotting.Results: The Y-maze, OLT, NORT, and MWM test demonstrated that SD-exposed rats exhibited cognitive dysfunction. SD triggered the elevation of hippocampal autophagy as evidenced by enhancement of autophagosome, up-regulations of beclin-1 and LC3 II/LC3 I, and down-regulation of p62. Meanwhile, the generation of endogenous H2S and the expressions of CBS and 3-MST (H2S producing enzyme) in the hippocampus of SD-treated rats were reduced.Conclusion: These results suggested that inhibition of endogenous H2S generation and excessiveness of autophagy in hippocampus are involved in SD-induced cognitive impairment.

Highlights

Sleep plays a key role in human life and work, but sleep deprivation (SD), namely irregular and inadequate sleep, shows a rising trend in today’s society (Feng et al, 2016; Honn et al, 2018)
The generation of endogenous H2S and the expressions of CBS and 3-mercaptopyruvate sulfurtransferase (3-MST) (H2S producing enzyme) in the hippocampus of SD-treated rats were reduced. These results suggested that inhibition of endogenous H2S generation and excessiveness of autophagy in hippocampus are involved in SD-induced cognitive impairment
The present study demonstrated that SD causes impairment in cognitive function, inhibition of hippocampal H2S generation, and excessiveness in hippocampal autophagy

Summary

Introduction

Sleep plays a key role in human life and work, but sleep deprivation (SD), namely irregular and inadequate sleep, shows a rising trend in today’s society (Feng et al, 2016; Honn et al, 2018). Extensive studies confirmed that rats deprived of sleep is embodied in various morphological and neurobiological changes in the brain and a decline of cognitive behavior (Zhang L. et al, 2013; Zhao et al, 2014; Hajali et al, 2015; Kreutzmann et al, 2015). Recent studies showed that the oxidative stress and the disorder of neurotransmitters play important roles in the cognitive impairment induced by SD (Lu et al, 2018; Nabaee et al, 2018; Siddique et al, 2018). We proposed that disturbances in hippocampal endogenous H2S generation and autophagy might be involved in SD-induced cognitive impairment

Methods

Results

Discussion

Conclusion