The Study Of Gsk-3?/?-Catenin/p-GluR 1 Underlying The Effects Of Early Life Stress On Anxiety- And Depression-like Behavior In Mice

Objectives: Early-life stress can lead to long-term consequence on cognitive,behavioral,and mood disorders in later life.Here,we assess the implications of an adverse early environment and the intervention of escitalopram or sodium valproate in different stages(infancy,adolescence and adulthood)on behavioral and hippocampal Gsk-3?/?-Catenin/ p-Glu R1 changes during adulthood in mice.And so as to study the pathophysiological mechanisms of early life stress,and provide a theoretical basis for the study of the pathogenesis of the early life stress-related diseases.Methods: In this study,a mouse model of maternal separation was adopted,the pregnant mice were divided into control group(CON)which was reared in normal condition,and early life stress group(ELS)whose mothers and themselves were experienced maternal separation from postnatal day 2 to day 21.Then,the saline,escitalopram and sodium valproate were administered separately to the mice during infancy,adolescence and adulthood in both the control group and the ELS group.We investigated behavioral and molecular changes resulting from ELS by measuring anxiety-like behavior in the open field test(OFT),social interaction test(SIT)and elevated plus maze(EPM)test,and depression-like behavior in tail suspension test(TST)and forced swimming test(FST),and the changes hippocampal Gsk-3?,p-Gsk-3?,?-Catenin,Non-phospho(Active)?-Catenin,Glu R1,p-Glu R1 and Glu R2 during adulthood in mice.Results: 1.In open field test,the distance moved during 10 minutes had no difference between each group,which demonstrated that neither early life stress,nor drug intervention in each stage had effect on motor activity in mice.In infancy intervention stage,ELS decreased time spent in center zone in mice,escitalopram intervention could increase the time spent in center zone.In adolescence intervention stage,ELS decreased time spent in center zone in mice,escitalopram or sodium valproate intervention could increase the time spent in center zone.In adult intervention stage,ELS decreased timespent in center zone in mice,escitalopram intervention could increased the time spent in center zone in ELS mice,however,escitalopram intervention decreased the time spent in center zone in CON mice.Stage curative effect revealed that sodium valproate intervention during adolescence stage could increase more time spent in center zone.2.In social interaction test,sodium valproate intervention could increase the distance moved during 10 minutes in social interaction box in infancy intervention stage.ELS decreased time spent in social interaction zone in mice,escitalopram or sodium valproate intervention could increase the time spent in social interaction zone in infancy intervention stage.In adolescence intervention stage,ELS decreased time spent in social interaction zone,escitalopram or sodium valproate intervention could increase the time spent in social interaction zone in ELS mice,but not in CON mice.In adult intervention stage,ELS decreased time spent in social interaction zone in mice,escitalopram intervention could increased the time spent in social interaction zone in CON mice,however,it couldn't increase the time spent in social interaction zone in ELS mice.Stage curative effect revealed that escitalopram intervention during adolescence stage could increase more time spent in social interaction zone.3.In elevated plus maze test,ELS decreased the distance moved in the elevated plus maze and the time spent in open arms,sodium valproate intervention could increase the distance moved in the elevated plus maze in infancy intervention stage.In adolescence intervention stage,ELS decreased the time spent in open arms,and sodium valproate intervention could increase the distance moved in the elevated plus maze.In adult intervention stage,sodium valproate intervention could increase the distance moved in the elevated plus maze and increased the time spent in open arms in ELS mice,but not in CON mice.4.In tail suspension test,ELS increased the immobility time and sodium valproate intervention could decrease the immobility time in infancy intervention stage.In adult intervention stage,ELS increased the immobility time in mice,but neither escitalopram,nor sodium valproate could reverse the effect of ELS.5.In forced swim test,escitalopram and sodium valproate intervention could decrease the immobility time in infancy intervention stage.In adult intervention stage,ELS increased the immobility time in mice,and sodium valproate also increased the immobility time in mice.Stage curative effect revealed that sodium valproate could reverse the effect of ELS only in infancy intervention stage.6.there areno difference in the expression of Gsk-3?,?-Catenin,Glu R1 and Glu R2 between each group.In infancy intervention stage,ELS decreased the expression of p-Gsk-3? and Non-phospho(Active)?-Catenin,and escitalopram and sodium valproate intervention could increase the expression of p-Gsk-3?,Non-phospho(Active)?-Catenin and p-Glu R1.In adolescence intervention stage,ELS decreased the expression of Non-phospho(Active)?-Catenin and p-Glu R1,and escitalopram and sodium valproate intervention could increase the expression of p-Gsk-3?.In adult intervention stage,ELS decreased the expression of p-Gsk-3?,Non-phospho(Active)?-Catenin and p-Glu R1,and escitalopram and sodium valproate intervention couldn't reverse the decreased the expression of p-Gsk-3?,Non-phospho(Active)?-Catenin and p-Glu R1 induced by ELS.Conclusion: Our study revealed that early life stress resulted in changes in the function of Gsk-3?/?-Catenin/p-Glu R1 signaling system,which increased the neurobiological vulnerability to stress in later life.