iveFunctional NR2B-containing NMDA receptors are formed by their coassembly with the obligatory NR1 subunit.Although NR1 subunits are ubiquitously expressed in the CNS,the localization of NR2B subunits are more restri...iveFunctional NR2B-containing NMDA receptors are formed by their coassembly with the obligatory NR1 subunit.Although NR1 subunits are ubiquitously expressed in the CNS,the localization of NR2B subunits are more restricted.NR2B subunits are found in the spinal cord,and localized predominantly in the forebrain.The more discrete distribution of NR2B subunits in the CNS gives hope that antagonists selective for this receptor subtype would retain the known analgesic properties of other NMDA receptor antagonists without the profound side-effect profile.Indeed,NR2B-slective compounds are antinociceptive in a variety of preclinical pain models and have a much lower side-effect profile compared with other NMDA receptor antagonists.Therefore,NR2B subunit in the CNS could serve as a new target site for controlling persistent pain in humans.展开更多
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...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。展开更多
文摘iveFunctional NR2B-containing NMDA receptors are formed by their coassembly with the obligatory NR1 subunit.Although NR1 subunits are ubiquitously expressed in the CNS,the localization of NR2B subunits are more restricted.NR2B subunits are found in the spinal cord,and localized predominantly in the forebrain.The more discrete distribution of NR2B subunits in the CNS gives hope that antagonists selective for this receptor subtype would retain the known analgesic properties of other NMDA receptor antagonists without the profound side-effect profile.Indeed,NR2B-slective compounds are antinociceptive in a variety of preclinical pain models and have a much lower side-effect profile compared with other NMDA receptor antagonists.Therefore,NR2B subunit in the CNS could serve as a new target site for controlling persistent pain in humans.
文摘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。
