前咽缺陷蛋白-1在APP／PS1转基因阿尔茨海默病小鼠模型中枢神经系统的分布及表达  

Distribution and expression of anterior pharynx-defective-1 in mice central nervous system of APP/PS1 transgenic Alzheime＇s disease model

作　　者：赵蕾[1] 龙志敏[1] 贺桂琼[1] 楚亚楠[1] 宋冲[1] 

机构地区：[1]重庆医科大学神经生物学重庆市重点实验室,400016

出　　处：《中华老年医学杂志》2011年第12期1038-1042,共5页Chinese Journal of Geriatrics

基　　金：国家自然科学基金（30700885）;教育部重点项目资助计划（209102）;重庆市首届优秀人才资助计划[渝教人（2009）2号];重庆市教委资助计划（KJ090328）;重庆医科大学重点课题资助项目（XBZD200702）

摘　　要：目的研究γ-分泌酶组件蛋白APH-1（anterior pharynx defective 1，APH-1）在成年APP／PS1双转基因痴呆小鼠中枢神经系统（central nervous system，cNs）中的分布及表达，以及在阿尔茨海默病（Alzheimer’s disease，AD）模型鼠和野生型小鼠脑中的表达差异，以进一步明确APH1与AD的关系。方法对APP／PS1双转基因AD模型种鼠交配后产下的子代进行基因分型，用免疫组化方法检测APH1在成年APP／PS1双转基因痴呆模型小鼠CNS内的分布及表达，以及比较APH-1在出生后1d、7d、21d、120d的痴呆小鼠及同窝野生型小鼠脑内的表达和分布情况。结果APH-1广泛分布于成年痴呆小鼠CNS的各区域，包括大脑皮质、海马、嗅脑、丘脑、纹状体、尾状核、中缝大核、小脑、脑干和脊髓等；出生1dAD模型鼠与同窝野生型小鼠大脑皮质内APH-1均有高水平表达，而出生7d、2id表达水平较低，且成年小鼠脑中其表达量有所回升；各时间点痴呆小鼠脑内APH-1免疫阳性反应都比同窝野生型小鼠显著增强（P〈0．05）。结论APH1在痴呆小鼠的CNS中广泛分布，但不同脑区分布和表达存在差异；且痴呆小鼠和正常野生型小鼠脑内APH-1分布和表达有区别，这些差异可能与AD的发生相关。Objective To investigate the distribution and expression of T-secretase subunit （APH-1） in the central nervous system （CNS） of APP/PS1 double transgenic Alzheimer＇s disease （AD） adult mouse model, and to detect the expression difference of APH-1 in developmental brain between AD model mouse and wild-type littermates in order to further clarify the relationship between APH-1 and AD. Methods Offspring bred by APP/PS1 double transgenie AD mice were genotyped. Immunohistochemical staining was used to detect APH-1 distribution and expression in the CNS of adult APP/PS1 double transgenic AD mouse model, in the brain of AD model mouse and its wild-type littermates on postnatal day 1, 7, 21 and 120. Results APH 1 was widely expressed in almost all regions of the CNS, especially in the cerebral cortex, hippocampus, olfactory bulb, hypothalamus, ventral striatum, caudate putamen, raphe magnus nucleus, cerebellum, brainstem and spinal cord of the adult APP/PS1 double transgenic mice. APH-1 expression was higher in the cortex of both AD and wild type mouse on postnatal day 1 than on postnatal day 7 and 21 with increased level of APH-1 protein in adult mouse brain. APH-1 expression in the brain of AD mice was higher than in its wild type littermates at any stage（P〈0.05）. Conclusions Distribution of APH-1 is ubiquitous and region-dependent in the CNS. The different distribution and expression between APP/PS1 double transgenie mouse model and its wild type lhtermate indicate that APH-1 may be related to AD.

关 键 词：淀粉样前体蛋白分泌酶类 中枢神经系统 阿尔茨海默病 

分 类 号：R749.16[医药卫生—神经病学与精神病学]