The Hippocampus Hsf1/hsp Role In The Psychological Stress-related Emotional And Cognitive

Part1 HSF1/HSP protect hippocampus and hippocampal -dependent function during chronic psychological stressOBJECTIVE To investigate the protect role of HSF1/HSP in hippocampus,and hippocampus-dependent emotion and working memory during chronic psychological stress.METHODS HSF1 gene knockout mice(HSF1-/- mice,n=56) and HSF1 gene wildtype mice(HSF1+/+ mice,n=56)were devided into 2 groups according to their genotype.In each group,mice were divided randomly into 4 groups:non-stress group(NS,n=14),heat shock stress group(HS,n=14),psychological stress group(PS,n=14),and heat shock stress plus psychological stress group(HS+PS,n=14).The NS group didn't receive any experimental stress.The HS group was submitted to heat shock stress.The PS group was submitted to psychological stress, including restraint stress,elevated open platform and communication box. The HS+PS group was submitted to heat shock stress preconditioning and then submitted to psychological stress.Animals were stressed from Monday to Saturday(not Sunday)for 8 weeks.24 hours after the last stress episode,2 mice in each group were deeply anaesthetized and killed, hippocampi removed,frozen in liquid nitrogen and stored for HSP72, HSP25,αBC,HSC70,Bcl-2 expression detection.At the same time, behaviour test was done in the rest of mice,then Brdu was injected.24 hour after the Brdu injection,mice were deeply anaesthetized and killed. The mice's brains were paraffin-embedded and cut in 5-μm-thick serial coronal sections starting at Bregma -1.7mm for detection of hippocampal apoptotic neurons and neurogenesis.RESULTS1.Effect of HSF1/HSR on emotional behavior during chronic psychological stressPsychological stress decrease percentage of time spent in open arms (P＜0.05)and total arm entries(P＜0.05)in elevated plus maze,decrease total number of squares acrossed in open field(P＜0.05),decrease total number of squares acrossed in noval cage(P＜0.05).Heat shock preconditioning inhibit the decrease of percentage of time spent in open arms(P＜0.05),total arm entries(P＜0.05)in elevated plus maze and total number of squares acrossed in noval cage(P＜0.05)in HSF1+/+ mice,but didn't inhibit the decrease of percentage of time spent in open arms (P＞0.05)and total arm entries(P＞0.05)in elevated plus maze,and didn't inhibit the decrease of total number of squares acrossed in noval cage in HSF1-/- mice(P＞0.05).2.Effect of HSF1 on working memory during chronic psychological stressPsychological stress didn't decrease correct alternation times in T maze in HSF1+/+ mice(P＞0.05),but decrease correct alternation times in HSF1-/- mice(P＜0.05).3.Effect of HSF1/HSR on locomotion and balance abilityPsychological stress increase time taken in bridge walking(P＜0.05) and decrease score in wire suspension test(P＜0.05)in both genotypes. Heat shock preconditioning didn't effect time taken in bridge walking (P＞0.05)and score in wire suspension test(P＞0.05).4.Effect of HSF1/HSP on hippocampal apoptosisExpression of HSP72,HSP25,αBC was higher in HSF1+/+ mice than in HSF1-/- mice.Heat shock preconditioning induce HSP72 in HS group and HS+PS group in HSF1+/+ mice.No difference of HSC70 expression was found between HSF1+/+ mice and HSF1-/- mice.Psychological stress induce CA3,CA1,DG neuron apoptosis in HSF1-/- mice(P＜0.05),and CA3 neuron apoptosis in HSF1+/+ mice (P＜0.05),but didn't increase CA1,DG neuron apoptosis in HSF1+/+ mice(P＞0.05).Heat shock preconditioning increase CA3,CA1,DG neuron apoptosis in HSF1-/- mice(P＜0.05),but decrease CA3,CA1 neuron apoptosis in HSF1+/+ mice(P＜0.05)and didn't effect DG neuron apoptosis in HSF1+/+ mice(P＞0.05).5.Effect of Psychological stress on hippocampal neurogenesisPsychological stress decrease hippocampal neurogenesis in HSF1+/+ mice and HSF1-/- mice(P＜0.05).CONCLUSION:1.Chronic psychological stress induce anxiety-like behavior and depressive-like behavior in mice.HSR active HSF1,induce HSP expression,inhibit the anxiety-like behavior and depressive-like behavior.2.Chronic psychological stress didn't impare working memory, Psychological stress active HSF1,induce HSP expression,and play an endogenous protective role in it.3.HSP protect hippocampal neuron from apoptosis during chronic psychological stress,and may underlying the mechanism of behavior improvement. Part 2 Role of HSF1 in spatial learning taskOBJECTIVE To investigate the potential involvement of HSF1 in spatial learning task.METHODS HSF1-/- mice(n=12)and HSF1+/+ mice(n=12) was trained in Morris water maze for 7 days,90 rain after the last training episode,mice were killed,hippocampi and prefrontal cortex removed, frozen in liquid nitrogen and stored for P-Erk1/2 expression detection.RESULTS The escape latency of HSF1-/- mice were signficantlly longer than HSF1+/+ mice in place navigation experiment in Morris water maze(P＜0.05).P-Erk1/2 expression in the hippocampi and prefrontal cortex were higher in HSF1+/+ mice than in HSF1-/- mice (P＜0.05).CONCLUSION HSF1 maintain the activation of Erk1/2 in hippocampus and prefrontal cortex,and play an important role in spatial learning task.