Expression Of NLRP1 Inflammasome-Autophagy-Associated Protein In Hippocampus Of Depressive--Like Mice

Depression is a common mental illness with high morbidity and mortality.The number of depression patients in the world is about 350 million,and it is on the rise year by year.By 2030,depression will become the first disease that endangers the physical and mental health of the masses and brings a heavy burden to the society.However,the pathogenesis of depression has not been fully clarified.The composition of NLRP1 inflammasome is a polyprotein complex composed of NLRP1,ASC, caspase-1 and others.The activation of NLRP1 inflammasome will further promote the release of inflammatory cytokines.This leads to inflammation.Autophagy is a "selfcleaning and phagocytosis" at the subcellular level,in which cells can be coated with monolayer or double-layer cell membranes to form autophagy.Then it is transported to lysosome to form autophagy lysosome,and then a variety of enzymes are degraded and digested,so as to realize the metabolism and renewal of the cell itself.The formation of autophagy begins with autophagy-associated proteins,which is regulated and coordinated by m TOR and P13K/Beclin-1 signals in the process of formation,in which LC3(microtubule associated protein 1 light chain 3)and its processing products LC3Ⅰ / LC3 Ⅱ(iconic molecule at the end of autophagy formation)play an important role in autophagy.Previous studies have shown that NLRP1 inflammasome and autophagy are involved in a variety of inflammatory nervous system diseases,but their role in depression has not been reported.The purpose of this study was to study the expression of NLRP1 inflammasome-autophagy associated proteins in the hippocampus of depressed mice in the hope of finding a new method for the treatment of depression.Objectives :Study of NLRP1 inflammasome and its associated inflammatory cytokines and autophagy under stimulation of Chronic Social Defeat Stress(CSDS)and repeated Repeat Social Defeat Stress(RSDS)-induced expression in hippocampus of depressivelike mice.Methods:The depression model of CSDS,RSDS mice was established.The changes of depressive-like behavior induced by stress were observed by social contact test,light and dark preference experiment,open field test(OFT),forced swimming test(FST)and tail suspension test(TST).Western blot and Real-time PCR were used to detect the expression of NLRP1,ASC and Caspase-1 in the hippocampus of each experimental group of mice,and Western blot method was used to detect the inflammatory cytokines IL-18,IL-6.Expression of IL-1 β and TNF-α and autophagy-associated proteins LC3,ATG5,ATG7,and Beclin-1 in hippocampus of each experimental group of mice.Results:1.Compared with the control group,the immobility time of tail suspension,forced swimming of mice in CSDS group increased significantly and the social contact rate was decreased significantly after stimulation with CSDS stress,The results of motion distance evaluation,average velocity evaluation,thread penetration number evaluation and standing number evaluation were also significantly reduced.In addition,compared with the control group,the expression of inflammasome complexes such as NLRP1,Caspase-1,and ASC in the hippocampus of CSDS group was significantly increased,and the expression of inflammatory cytokines IL-6,IL-18,IL-1 β and TNF-αwere also significantly increased.The expression of autophagy-associated proteins ATG5,ATG7,Beclin-1 and LC3Ⅱ/LC3Ⅰwere significantly decreased.2.Compared with the control group,the immobility time of tail suspension and forced swimming of mice in RSDS group increased significantly and in the light and dark preference test,the time spent in the bright place was also less than that in the control group after stimulation with RSDS.The results of motion distance evaluation,average velocity evaluation,thread penetration number evaluation and standing number evaluation were also significantly reduced.In addition,compared with the control group,the expression of inflammasome complexes NLRP1,Caspase-1and ASC in the hippocampus of RSDS group was significantly increased,and the expression of inflammatory cytokines IL-6,IL-18,IL-1 β and TNF-α were also significantly increased.The expression of autophagy-associated proteins,ATG5,ATG7,Beclin-1and LC3Ⅱ/LC3Ⅰ were significantly decreased.Conclusion:In the hippocampus of chronic social defeat stress and repeated social defeat stress-induced depressive-like mice,the expression of NLRP1 inflammasome and inflammatory cytokines were up-regulated,while the expression level of autophagyassociated proteins were significantly decreased.These results suggested that NLRP1inflammasome-autophagy signal may play an important role in stress-induced depressive-like behavior in mice.