Chronic Stress Induced Asymmetric Autophagy In Rat Hippocampus

Objectives: The volume of the hippocampus and the apoptosis rate of neurons are asymmetrically changed under chronic stress,which may be related with the autophagy of hippocampus,but the effects of different stressors on the autophagy of hippocampus and the asymmetric differences between left and right hippocampus are not studied deeply.Therefore,this study established a chronic psychological stress model and a chronic pain stress model to explore(1)the behavior changes under two models,(2)the change of autophagy induced in two models,(3)the asymmetric change of autophagy and related signaling pathway in two models.Methods: Male Sprague-Dawley rats were randomly divided into four groups,including control group,CUMS group,sham group and SNI group.After the chronic psychological stress model and chronic pain stress model were established,to evaluate the behaviors and mechanical pain sensitivity after 35 days,all groups were subjected to evaluate weight,sucrose preference test and Von Frey test.Further,we observed the effects of chronic stress on the autophagy process of hippocampus in four groups of rats by transmission electron microscopy,and further study on whether there were changes about autophagy in the bilateral hippocampus of rats by observing the expressions of autophagy related protein(LC3-II,p62)and phosphorylated mTOR signaling protein(p-mTOR)analyzed with western blot.And we also explored the difference between the effects of two models on hippocampal autophagy in rats.Results:(1)Chronic psychological stress caused weight loss and decreased preference for sucrose in rats.Moreover,chronic psychological stress and chronic pain stress increased the sensitivity of mechanical pain in rats.(2)Chronic psychological stress caused the expressions of LC3-II protein and p62 protein in the right hippocampus decreased,and these changes were not significant in the left hippocampus.p62 protein in the right hippocampus was significant increased in chronic pain stress model,but the expression of LC3-II protein did not increased in the right hippocampus.(3)p-mTOR protein decreased in the right hippocampus under chronic psychological stress,and the change was not significant in the left hippocampus.Chronic pain stress did not induce significant change in the expression of p-mTOR protein in the bilateral hippocampus.Conclusions:(1)Chronic psychological stress and chronic pain stress can change animal behaviors and increase mechanical pain sensitivity in rats,which means the general adaptation change.The common behavioral changes can become behavioral indicators of chronic stress.(2)Chronic psychological stress and chronic pain stress have specific effects on the process of autophagy of hippocampal in rats.In chronic psychological stress model,the activation of mTOR was inhibited,and autophagy flux was enhanced,so the autophagy is excessive,but in chronic pain stress model the autophagy flux was impaired.(3)two kinds of chronic stress models induce asymmetric autophagy between left and right brain and the right brain is more vulnerable to stress under current experimental conditions.