谷氨酸受体与γ-氨基丁酸_A受体在APPswe转基因小鼠海马结构中的表达  

Expression of glutamate receptors and GABA_A receptors in the hippocampus of APPswe transgenic mice

作　　者：范文娟[1] 席艳[1] 程维杰 牛艳丽[1] 于东明[1] 邓锦波[1] 

机构地区：[1]河南大学神经生物学研究所河南大学神经生物学实验室,开封475004

出　　处：《解剖学报》2010年第3期333-338,共6页Acta Anatomica Sinica

基　　金：国家自然科学基金面上项目(30771140;30670688);河南省教育厅自然科学研究项目(2007180008);河南省科技厅国际协作项目(0646630014);河南大学校内基金项目资助(07YBZR015)

摘　　要：目的探讨谷氨酸受体和γ-氨基丁酸A(GABAA)受体在阿尔茨海默病(AD)发生、发展中的作用。方法利用免疫荧光技术标记正常及APPswe转基因小鼠P0至P360各年龄段海马CA3区N-甲基-D-天门冬氨酸受体亚单体1(NMDAR1)、GluR2/3和GABAARα1-6阳性细胞,并利用免疫印迹法对海马组织内NMDAR1和GABAARα1-6的活化片段进行半定量分析。结果在模型组与对照组小鼠海马CA3区,NMDAR1、GluR2/3和GABAARα1-6在出生后P7时明显增加,P30达到高峰,以后逐渐下降至成年水平;与同龄对照组相比,老龄(P360)模型鼠NMDAR1和GluR2/3阳性细胞密度明显减少(P<0.05),而GABAARα1-6阳性细胞密度变化不明显(P>0.05)。免疫印迹法检测结果与免疫荧光技术统计结果吻合。结论 NMDAR1和GluR2/3表达下降与AD相关的神经退行性疾病有关;而GABAARα1-6在AD发病中的作用尚不能确定。Objective In order to understand the relationship between the receptors of excitatory and inhibitory neurotransmitter and Alzheimer disease （AD） , the expression of glutamate receptors and GABAAα1-6 in the CA3 region of hippocampus of APPswe transgenie mice was investigated. Methods These mice from postnatal day 0 to postnatal day 360 were used in the study with the N-methyl-D-asprtate receptor 1 （ NMDAR1 ） , GluR2/3 and GABAAα1-6 immunofluoreseent stainings. In the meantime, Western blotting was carried out to detect the expressions of NMDAR1 and GABAAα1-6 in the hippocampus as well. Results The numbers of NMDAR1, GluR2/3 and GABAAα1-6 positive neurons increased obviously after P7, in both wild type and transgenic mice, with the peaks at P30. However, in aged animals（P360） , NMDAR1 and GluR2/3 lost in transgenie mice with statistically significant difference （ P 〈 0. 05 ） , comparing with wild type, but the alterations of GABAAα1-6 receptor was not obvious （P 〉 0. 05） between wild type and transgenie mice. Conclusion The study showed that glutamate receptors in hippoeampus may play an important role in the development of Alzheimer disease, however the function of GABAA receptors needs to be studied further.

关 键 词：阿尔茨海默病 发育 谷氨酸受体 Γ-氨基丁酸受体 免疫荧光 小鼠 

分 类 号：R322.8[医药卫生—人体解剖和组织胚胎学]