经颅直流电刺激促进小鼠脑缺血后海马神经发生涉及NMDA受体上调  

Transcranial direct current stimulation promotes hippocampal neurogenesis in mice with cerebral ischemia involving up-regulation of NMDA receptors

作　　者：马晓娇 承欧梅[2] 校欢 宋丹[2] 蒋青松[1] 邱红梅[1] MA Xiao-jiao;CHENG Ou-mei;XIAO Huan;SONG Dan;JIANG Qing-song;QIU Hong-mei(Dept of Pharmacology,Chongqing Key Lab of Biochemistry and Molecular Pharmacology Medical University,Chongqing 400016,China;Dept of Neurology,the First Affiliated Hospital of Chongqing Medical University,Chongqing 400016,China)

机构地区：[1]重庆医科大学药理学教研室,重庆市生物化学与分子药理学重点实验室,重庆400016 [2]重庆医科大学附属第一医院神经内科,重庆400016

出　　处：《中国药理学通报》2020年第2期175-181,共7页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 81871002,81471334,81100981);重庆市自然科学基金资助项目(No cstc2017jcyjA0482)。

摘　　要：目的探讨经颅直流电刺激(transcranial direct current stimulation,tDCS)促进脑缺血小鼠内源性海马神经发生的作用及其可能机制。方法采用双侧颈总动脉夹闭法建立小鼠急性脑缺血模型,HE染色检测小鼠海马病理形态学改变;Morris水迷宫以检测小鼠学习记忆功能;免疫荧光染色观察海马区BrdU、DCX以及BrdU/NeuN阳性细胞表达以检测小鼠海马神经发生;以qRT-PCR和Western blot法分别检测小鼠海马NMDAR亚基NR2a、NR2b的mRNA及蛋白表达。结果脑缺血小鼠海马CA1区神经元损伤明显(P<0.01),学习记忆功能显著下降(P<0.01),提示脑缺血模型成功建立。同时,海马BrdU,DCX和BrdU/NeuN阳性细胞表达明显增加(P<0.01),表明脑缺血后海马出现神经发生。tDCS治疗后可显著改善CA1区病理损害,提高学习记忆能力,并促进神经发生。同时,海马NR2a、NR2b的mRNA及蛋白表达水平也上调(P<0.05或P<0.01)。结论tDCS可促进脑缺血后小鼠海马神经发生,改善学习记忆功能,其机制可能与上调NR2a、NR2b表达相关。Aim To investigate the improving effect of transcranial direct current stimulation(tDCS)on endogenous hippocampal neurogenesis in mice with cerebral ischemiaand the possible mechanism.Methods The model of acute cerebral ischemia in mice was established by bilateral common carotid artery occlision(BCCAO).The pathological changes of mice were detected by hippocampal HE staining.The learning and memory function of mice was assessed by Morris water maze.The number of BrdU,DCX and BrdU/NeuN-positive cells was observed through immunofluorescence staining for detecting hippocampal neurogenesis.The mRNA and protein expressions of NMDAR subunits NR2a and NR2b in hippocampus were detected by qRT-PCR and Western blot.Results The neuronal damage in the hippocampal CA1 region was marked(P<0.01),and the learning and memory function significantly decreased(P<0.01)in cerebral ischemia mice,suggesting the successful establishment of cerebral ischemia model.At the same time,the number of BrdU,DCX and BrdU/NeuN positive cells was up-regulated significantly(P<0.01),indicating the occurrence of neurogenesis in hippocampus after cerebral ischemia.Treatment with tDCS significantly ameliorated the pathological damage in CA1 region of mice,improved learning and memory,and promoted hippocampal neurogenesis.Meanwhile,the mRNA and protein expression levels of NR2a and NR2b in hippocampus were also up-regulated(P<0.05 or P<0.01).Conclusions tDCS can promote hippocampal neurogenesis and improve learning and memory function in cerebral ischemia mice,which may be related to theup-regulation ofNR2a and NR2b expression.

关 键 词：脑缺血 海马 神经发生 TDCS NR2A NR2B 

分 类 号：R-332[医药卫生] R322.81