慢性应激诱发APP/PS-1双转基因阿尔茨海默病小鼠认知损害研究  

Chronic stress induced cognitive impairment in APP/PS-1 double transgenic mouse model of Alzheimer's disease

作　　者：韩冰[1] 耿媛[1] 沈莉[2] 孙美玉[1] 王倩[1] 王铭维[1] 

机构地区：[1]河北医科大学第一医院神经内科河北省脑老化与认知神经科学重点实验室,石家庄050031 [2]河北医科大学第一医院检验科,石家庄050031

出　　处：《中国现代神经疾病杂志》2015年第8期631-637,共7页Chinese Journal of Contemporary Neurology and Neurosurgery

基　　金：国家重点基础研究发展计划(973计划)前期研究专项课题(项目编号:2010CB535005);河北省重大医学科研课题(项目编号:zd2013079);河北省自然科学基金资助项目(项目编号:H2015206238)~~

摘　　要：目的观察慢性应激对APP/PS-1双转基因阿尔茨海默病(AD)小鼠认知功能和脑组织形态学的影响,探讨环境因素的作用机制。方法采用Morris水迷宫实验评价C57BL/6小鼠(正常对照组,15只)和APP/PS-1双转基因小鼠[27只,包括AD组(13只)和AD+慢性不可预知性温和应激(CUMS)组(14只)]空间学习和记忆能力,刚果红染色观察海马组织淀粉样蛋白沉积,透射电子显微镜观察海马CA1区神经元超微结构。结果与正常对照组相比,AD+CUMS组小鼠Morris水迷宫实验逃避潜伏期延长[(33.14±14.37)s对(21.22±12.16)s;t=-2.701,P=0.045],平台象限停留时间缩短[(9.74±1.35)s对(15.02±1.33)s;t=2.639,P=0.012]。与AD组相比,AD+CUMS组小鼠淀粉样斑块面积占海马面积百分比增加[(0.59±0.03)%对(0.04±0.03)%;t=-2.900,P=0.005]。AD组小鼠海马神经元超微结构轻度受损,表现为神经元胞膜尚完整,胞质基质尚均匀,细胞内出现脂褐素,胞核和核膜结构尚可,线粒体嵴膜融合,高尔基体部分模糊,内质网轻度扩张;AD+CUMS组小鼠海马神经元超微结构受损明显,表现为胞膜部分模糊不清,胞质苍白,基质不均匀,各种细胞器数目均减少,细胞内可见较多脂褐素和自噬小体,胞核内染色质边集、核膜模糊,线粒体嵴膜融合严重,核糖体数目明显减少。结论慢性不可预知性温和应激是阿尔茨海默病小鼠认知损害的诱发因素,可以加重海马神经元的病理改变。Objective To observe the effect of chronic unpredictable mild stress（CUMS） on thecognitive function and brain morphological changes in APP/PS-1 mice, one of the genetic mouse models ofAlzheimer＇s disease（AD）, and to investigate the possible role of environmental factors in genetic mousemodel of AD.Methods There were 22-week-old wild-type C57BL/6 male mice（control group, N = 15）and APP/PS-1 double transgenic male mice [N = 27： AD group（N = 13） and AD ＋ CUMS group（N = 14）]tested in this study. Morris water maze test was used to evaluate spatial learning and memory of the mice.Amyloid deposition in the hippocampus was determined by Congo red staining. The ultrastructure ofneurons in hippocampal CA1 region was observed by transmission electron microscope（TEM）.Results Compared with control group, AD ＋ CUMS group had significantly longer fifth-day escape latency [（33.14 ±14.37） s vs（21.22 ± 12.16） s; t =- 2.701, P = 0.045], and significantly shortened time spent in platformquadrant [（9.74±1.35） s vs（15.02 ± 1.33） s; t = 2.639, P = 0.012] in Morris water maze test. Compared with AD group, the percentage of amyloid plaque area in hippocampal area was increased in AD ＋ CUMS group[（0.59 ± 0.03）% vs（0.04 ± 0.03）%; t =- 2.900, P = 0.005]. The ultrastructure of hippocampal neurons in ADgroup was slightly damaged： cellular membrane was intact; cell matrix was uniform; intracelluar lipofuscincould be seen; the structure of nucleus and nuclear membrane had no obvious changes; mild fusion ofcristae and membrane was seen in mitochondria; Golgi apparatus was partially indistinct; endoplasmicreticulum was mildly expanded. The ultrastructure of hippocampal neurons in AD ＋ CUMS group wasobviously damaged, including blurred cell membrane, reduced low- density and high- density granules incytoplasm, uneven cell matrix, reduced number of organelles, lipofuscin and autophagosome deposition,obvious condensation of chromatin distributing over the fringe of nuclei, blurred n

关 键 词：应激 阿尔茨海默病 认知障碍 显微镜检查 荧光 显微镜检查 电子 透射 疾病模型 动物 

分 类 号：R749.16[医药卫生—神经病学与精神病学]