Effects Of Calpain I-Cdk5Pathway On Prop-ofol Alleviating Depressed Rats’ Learning/Memory Impairment Induced By Electro-Convulsive Therapy

Objiective To investigate the effects of depressed beheavior, learningand memory, calpain I and cyclin-dependent kinase5(Cdk5) in hippocampusof depressed rats undergoing electroconvulsive therapy(ECT), so as to studythe possible mechanism of propofol reducing the impairment of learningmemory induced by ECT.Methods Fifty healthy adult male Sprague-Dawley rats,12weeks,weighing211±17g，were randomly divided into5groups (n=10per group):control group (group C), depression group (group D), propofol group (groupDP), ECT group (group DE), propofol combined with ECT group (groupDPE). All rats except group C were stressed repeatedly for28days toestablish depressed model. After the model was set up, rats of group DEwere treated with ECT once a day for one week and group DPE weretreated with ECT pretreated with intraperitoneal injection of propofol once aday for one week. Open-field test was used to assess depressive state. Morriswater maze was used to assess learning memory.The expressions of calpain I and CaMKII proteins were detected using immunohistochemistry,respectively. The expression of Cdk5protein was detected usingwestern-blot and its activity was analyzed with a liquid scintillation counter.The expressions of calpain I and Cdk5mRNA were detected using RT-PCR,respectively.Results (1) Open-field test: Pre-model, there was no significantdefference among each group (P>0.05). Post-model, compared with group C,the total distance and rearing number derecreased（P<0.05）and there was nosignificant defference among the other4groups(P>0.05). After treatment：compared with group C, the total distance and rearing number derecreased inthe other4groups and there was no difference between group D and DPand between group DE and DPE(P>0.05).(2) Sucrose preference test: Pre-model, there was no significantdefference among each group (P>0.05). Post-model, compared with groupC, the sucrose preference percentage (SPP) derecreased（P<0.05）and therewas no significant defference among the other4groups(P>0.05). Aftertreatment：compared with group C, the SPP derecreased in the other4groupsand there was no difference between group D and DP and between groupDE and DPE(P>0.05).(3) Learning/memory capability: Pre-model, there was no significantdefference among each group (P>0.05). Post-model, compared with group C, the escape latency (EL) prolonged and space exploration time (SET)shortened in the other4groups (P<0.05) and there was no difference in theother4groups (P>0.05). After treatment, compared with group D, group DEexhibited the EL prolonged (P<0.05) and SET shortened (P<0.05), groupDPE exhibited the EL shortened (P<0.05) and SET prolonged (P<0.05);Compared with group DE, group DPE exhibited the EL shortened (P<0.05)and SET prolonged (P<0.05); however, there was no difference betweengroup D, DP and DPE (P>0.05).(4) The expression of calpain I in hippocampus: compared with groupC, the expression of calpain I protein and mRNA in hippocampus in theother groups exhibited that increased in group DE and DPE increased(P<0.05); compared with group D, the expression of calpain I protein andmRNA in group DE increased; compared with group DE, calpain I proteinand mRNA in group DPE decreased (P<0.05).(5) The expression of Cdk5in hippocampus: compared with group C,the other groups exhibited that Cdk5activity up-regulated and the Cdk5protein and mRNA in group DE and DPE increased (P<0.05); comparedwith group D, group DE exhibited that t the expression of Cdk5protein andmRNA in hippocampus increased and Cdk5activity up-regulated, groupDPE exhibited that Cdk5protein and mRNA in hippocampusincreased(P<0.05); compared with group DE, group DPE exhibited that Cdk5protein and mRNA in hippocampus decreased, Cdk5activitydown-regulated (P<0.05).(6) The expressions of CaMKII and pCaMKII in hippocampus:compared with group C, the other groups exhibited that the expressions ofCaMKII and pCaMKII decreased (P<0.05); compared with group D,group DE exhibited that the expressions of CaMKII and pCaMKIIdown-regulated and the ratio of pCaMKII/CaMKII decreased, group DPEexhibited that the expression of pCaMKII up-regulated (P<0.05);compared with group DE, group DPE exhibited that the expressions ofCaMKII and pCaMKII up-regulated and and the ratio ofpCaMKII/CaMKII increased (P<0.05).Conclusions (1) ECT treatment can improve depressive behavior ofrats, but it can cause severe learning/memory impairment. It was related tothe impairment of calpain I-Cdk5pathway.(2) Propofol combined with ECT can improve depressive behavior ofrats and alleviate learning/memory impairment. It was related that propofolreversed the ECT-induced impairment of the calpain I-Cdk5pathway tosome extent.