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早期APP/PS1转基因AD模型小鼠海马胆碱能神经元改变的体视学研究
引用本文:李常琼,晁凤蕾,张蕾,唐静,蒋林,张毅,周春妮,黄维,唐炜,李桃,赵振华,唐勇,吴宏. 早期APP/PS1转基因AD模型小鼠海马胆碱能神经元改变的体视学研究[J]. 第三军医大学学报, 2017, 39(6). DOI: 10.16016/j.1000-5404.201610046
作者姓名:李常琼  晁凤蕾  张蕾  唐静  蒋林  张毅  周春妮  黄维  唐炜  李桃  赵振华  唐勇  吴宏
作者单位:400016重庆,重庆医科大学基础医学院人体解剖与组织胚胎学教研室,干细胞与组织工程研究室
基金项目:国家自然科学基金面上项目,重庆市首批“百名学术学科领军人才”培养计划,重庆医科大学优秀博士论文资助项目,重庆市研究生科研创新项目(2016)Supported by the General Program of National Natural Science Foundation of China,the Project of the First Batch of "100 Academic and Discipline Talented Leaders" of Chongqing,the Foundation of Excellent Doctoral Dissertation of Chongqing Medical University,the Innovative Fund for Graduate Student of Chongqing
摘    要:
目的 应用体视学方法定量研究APP/PS1双转基因AD模型小鼠海马内胆碱能神经元的早期改变情况.方法 Morris水迷宫检测10月龄雌性APP/PS1双转基因AD小鼠(APP/PS1组)和同月龄同窝生雌性野生型小鼠(Wild-type组)的空间学习记忆能力.运用现代体视学方法结合免疫组织化学方法精确定量小鼠海马各亚区的体积和胆碱能神经元的数量.结果 APP/PS1组小鼠定位航行实验中逃避潜伏期长于Wild-type组(P<0.01).空间探索实验中,APP/PS1组小鼠穿越平台的次数及平台所在象限时间百分比均少于Wild-type组(P=0.007、0.041).APP/PS1组小鼠海马齿状回(dentate gyrus,DG)的体积较Wild-type组缩小(P =0.001),而APP/PS1组小鼠海马CA1、CA2/3区的体积较Wild-type组差异无统计学意义(P =0.089、0.059).APP/PS1组小鼠海马DG内胆碱能神经元的数量较Wild-type组显著减少(P=0.017),APP/PS1组小鼠海马CA1区、CA2/3区内胆碱能神经元较Wild-type组差异均无统计学意义(P =0.076、0.074).结论 早期APP/PS1双转基因AD小鼠海马DG内胆碱能神经元丢失,可能是AD早期出现空间学习记忆能力障碍的重要结构基础之一.

关 键 词:胆碱能神经元  齿状回  APP/PS1双转基因AD模型小鼠  体视学

Stereological study of cholinergic neurons in hippocampus of early-stage APP/PS1 Alzheimer's disease transgenic mice
Li Changqiong,Chao Fenglei,Zhang Lei,Tang Jing,Jiang Lin,Zhang Yi,Zhou Chunni,Huang Wei,Tang Wei,Li Tao,Zhao Zhenghua,Tang Yong,Wu Hong. Stereological study of cholinergic neurons in hippocampus of early-stage APP/PS1 Alzheimer's disease transgenic mice[J]. Acta Academiae Medicinae Militaris Tertiae, 2017, 39(6). DOI: 10.16016/j.1000-5404.201610046
Authors:Li Changqiong  Chao Fenglei  Zhang Lei  Tang Jing  Jiang Lin  Zhang Yi  Zhou Chunni  Huang Wei  Tang Wei  Li Tao  Zhao Zhenghua  Tang Yong  Wu Hong
Abstract:
Objective To investigate the early changes of cholinergic neurons in the hippocampus of APP/PS1 Alzheimer's disease (AD) transgenic mice.Methods Ten-month-old female APP/PS1 AD transgenic mice and age-matched littermate wild-type female mice were used.The spatial learning and memory abilities were tested with Morris water maze.The quantitative calculations for the volume of hippocampal subregions and the number of the cholinergic neurons in hippocampal sub-regions were obtained using the stereological methods.Results The escape latency time of the APP/PS1 transgenic group was significantly longer than that of the wild-type group (P < 0.01).There were significant differences in the times of the platform location crosses and the time spending in the target quadrant between the wild-type group and the APP/PS1 transgenic group (P =0.007,P =0.041).The volume of the dentate gyrus and the number of the cholinergic neurons in the dentate gyrus were significantly reduced in the APP/PS1 transgenic group as compared with the wild-type group (P =0.001,P =0.017).The volume of the CA1 and CA2/3 sectors and the number of the cholinergic neurons in the CA1 and CA2/3 sectors were not significantly changed in the APP/PS1 transgenic group as compared with the wild-type group (P =0.089,P =0.059,P =0.076,P =0.074).Conclusion The loss of the cholinergic neurons in the dentate gyrus may be one of the morphological bases for the behavior deficits of the early-stage APP/PS1 AD transgenic mouse.
Keywords:cholinergic neurons  dentate gyrus  APP/PS1 AD transgenic mice  stereology
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