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MK-801 or DNQX reduces electroconvulsive shock-induced impairment of learning-memory and hyperphosphorylation of Tau in rats

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Author:: No author available

Journal Title:: Acta Physiologica Sinica

Issue:: 4

DOI:: No doi available

Key Word:: 兴奋性氨基酸受体拮抗剂;电休克;学习记忆能力;Tau蛋白;过度磷酸化;谷氨酸

Abstract：本研究通过观察兴奋性氨基酸受体拮抗剂对电休克(electroconvulsive therapy,ECT)后Wistar-Kyoto(WKY)抑郁大鼠模型学习记忆和Tau蛋白过度磷酸化的影响,探讨兴奋性氨基酸受体拮抗剂对Tau蛋白过度磷酸化的调节及两者对抑郁大鼠学习记忆的影响,以期为改善ECT后学习记忆障碍的神经心理学机制研究和临床干预性治疗提供实验依据.按随机单位组析因设计设置2个干预因素,即电休克干预(两水平:无处置、施行1疗程ECT)和兴奋性氨基酸受体拮抗剂干预(三水平:注射生理盐水、NMDAR拮抗剂MK-801、AMPAR拮抗剂DNQX)的所有组合(2 × 3析因设计)进行实验.将48只24周-WKY大鼠随机分为6组(n=8):生理盐水组(经尾静脉注射2 mL生理盐水)、MK-801组(经尾静脉注射2 mL 5 mg/kg MK-801)、DNQX组(经尾静脉注射2 mL 5 mg/kg DNQX)、生理盐水+ECT组(经尾静脉注射2 mL生理盐水+施行1疗程ECT)、MK-801+ ECT组(经尾静脉注射2 mL 5 mg/kg MK-801+施行1疗程ECT)、DNQX+ ECT组(经尾静脉注射2 mL 5 mg/kg DNQX+施行1疗程ECT).全部ECT处置结束24 h内开始Morris水迷宫检测,然后留取各组大鼠海马组织.高效液相色谱法检测海马组织中神经递质Glu含量；免疫组织化学SP法和Western blot检测Tau5(总Tau蛋白)、p-PHF1Ser396/404、p-AT8Ser199/202、p-12E8Ser262在海马组织中的表达.结果显示,ECT和Glu离子型受体(NMDAR、AMPAR)均可造成大鼠学习记忆障碍,即延长逃避潜伏期,并缩短空间探索时间；ECT和Glu受体GluR拮抗剂合用之后,其造成的大鼠学习记忆障碍程度反而减轻.ECT可明显增加海马中Glu的浓度；GluR拮抗剂对海马中Glul的浓度没有明显影响.ECT和GluR拮抗剂对海马总Tau蛋白表达无明显影响.ECT可增加海马中磷酸化Tau蛋白的表达；GluR拮抗剂可减少海马中磷酸化Tau蛋白的表达；两者合用的影响呈相减效果,即GluR拮抗剂可使ECT造成的海马磷酸化Tau蛋白的表达增加的幅度降低.以上结果表明,ECT导致海马Glu浓度升高,Glu激动NMDAR和AMPAR,从而增加海马Tau蛋白的磷酸化程度,从而导致学习记忆功能障碍.

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