| Objective This explored the protective effect of propofol on the spatial learning and memory function and regulating the expression ofγ-aminobutyric acid type A receptors(GABA_AR)and its ligandγ-aminobutyric acid(GABA)protein in hippocampus of depression model rats after electroconvulsive shock(ECS),with the aim to investigate the effect of GABA_AR on synaptic plasticity in the brain protection of depression rats after ECS.MethodsPARTⅠTwelve Sprague Dawley(SD)male,healthy,2-3 months old rats were selected as the control group(Group C).In addition,36 successfully established CUMS(chronic unpredictable mild stress,CUMS)model rats in the same nest were randomly divided into three groups(n=12):depression group(group D),ECS treatment group(group E)and propofol combined ECS group(group EP).The normal rats in group C and the depressed rats in group D were not given any treatment;the depressed rats in Group E were given electroconvulsive shock(ECS);the depressed rats in group ME were given modified electric convulsive therapy(MECT).The measures are specifically as follows:rats in group C and D were treated with sham ECS after intraperitoneal injection of 8ml/kg saline;rats in Group E were treated with ECS after intraperitoneal injection of 8ml/kg saline;rats in group EP were treated with ECS after intraperitoneal injection of 80mg/kg propofol with concentration of 1%.The above treatment is once a day for 7consecutive days.The depressive behaviour of rats was assessed by the sucrose preference test(SPT);the spatial learning and memory function of rats was assessed by the Morris water maze(MWM);the concentration of GABA in hippocampus was measured by ELISA;the protein expression ofα5-GABA_AR in hippocampus was observed by Western-blot and immunohistochemistry.PARTⅡ36 successfully established CUMS model depressive rats were randomly divided into three groups(n=12):depression group(group D),electroconvulsive shock group(group E)and electroconvulsive shock+antagonist bicuculline group(group EB).6 rats of each group were established SPT and MWM,and another 6 rats of each group were sacrificed for the hippocampal slices prepared from the brain tissue of rats.The long-term potentiation(LTP)were recorded by electrophysiology.ResultsPARTⅠ(1)Depression-like behavior test of rats:after modeling,there was statistical difference in sucrose preference percentage(SPP)in each group(F=142.19,P<0.05).The SPP of group D,group E and group EP was lower than that of group C(P<0.05),but there was no statistic difference between group D,group E and group EP(P>0.05).After the treatment,there was statistical difference in SPP(F=133.21,P<0.05).The SPP of group D,group E and group EP was lower than that of group C(P<0.05);the SPP of group E and group EP was higher than that of group D(P<0.05);the difference of SPP between group E and group EP was not statistically significant(P>0.05).(2)Detection of spatial learning and memory ability in rats:there was no significant difference in swimming speed between the groups(F=0.86,P>0.05).There was significant difference between escape latency(F=5.59,P<0.05)and space exploration time(F=27.95,P<0.05).Group D,group E and group EP had longer escape latency(P<0.05)and shorter space exploration time(P<0.05)than that of group C;group E and group EP had longer escape latency(P<0.05)and shorter space exploration time(P<0.05)than that of group D;group EP had shorter escape latency(P<0.05)and longer space exploration time(P<0.05)than that of group E.(3)Detection of GABA concentration in hippocampus of rats:there was a significant difference in GABA content between the hippocampus of each group(F=200.69,P<0.05).The GABA content in hippocampus of group D was lower than that of group C(P<0.05),and that of other groups was higher than that of group C(P<0.05);the GABA level of group E and group EP was higher than that of group D(P<0.05);the GABA level of group EP was lower than that of group E(P<0.05).(4)Expression ofα5-GABA_AR protein in rat hippocampus(Western-blot):there was significant difference in the relative expression level ofα5-GABA_AR in hippocampus(F=200.69,P<0.05).The expression ofα5-GABA_AR in group D was lower than that in group C(P<0.05);more in Group E and EP than in group C(P<0.05);more in Group E and EP than that in group D(P<0.05);more in group EP than that in Group E(P<0.05).(5)The distribution and expression ofα5-GABA_AR in rat hippocampus(immunohistochemistry):the expression ofα5-GABA_AR in hippocampus of group D was lower than that of group C,while that of group E and EP was higher than that of group C.The expression and distribution ofα5-GABA_AR in group EP was significantly higher than that of group E.The positive expression rate ofα5-GABA_AR protein in CA1 area of hippocampus(F=43.38,P<0.05)was statistically significant.The expression ofα5-GABA_AR in group D was lower than that in group C(P<0.05);Group E and group EP were higher than group C(P<0.05),Group E and group EP were higher than group D(P<0.05);group EP was higher than Group E(P<0.05).PARTⅡ(1)Sucrose preference test:the difference of SPP before and after CUMS modeling was statistically significant(F=208.38,P<0.05).After ECS treatment,the difference of SPP in each group was statistically significant(F=183.31,P<0.05).Compared with group D,the SPP in group E and group EB was higher(P<0.05);compared with group E,the difference in group EB was not statistically significant(P>0.05).(2)Morris water maze:there was no significant difference in swimming speed between the groups(F=0.35,P>0.05).There was significant difference between escape latency(F=9.23,P<0.05)and space exploration time(F=34.24,P<0.05).Group E and group EB had longer escape latency(P<0.05)and shorter space exploration time(P<0.05)than that of group D;group E had longer escape latency(P<0.05)and shorter space exploration time(P<0.05)than that of group EB.(3)The LTP in the SC-CA1 pathway in rat hippocampus:the difference of LTP in hippocampus of each group was statistically significant(F=91.99,P<0.05).The LTP of group E and group EB was significantly lower than that of group D(P<0.05),and that of group EB was significantly lower than that of group E(P<0.05).Conclusions(1)Propofol alleviated the learning and memory impairment caused by ECS through up-regulating the expression ofα5-GABA_AR in hippocampus with enhanced inhibitory effect mediated by GABA.(2)Propofol reduced the learning and memory impairment of depression rats after ECS possibly through activating GABA_AR to inhibit the over activation of NMDAR and protecting LTP. |
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