早老素增强子-2在APP／PS1双转基因小鼠脑内的分布及表达  

Expression and distribution of presenilin enhancer-2 in brain of APP/PS1 double transgenic mice

作　　者：楚亚楠[1] 宋冲[1] 贺桂琼[1,2] 刘刚[1] 王凌晞[1] 周泽芬[1] 

机构地区：[1]重庆医科大学神经科学研究中心,400016 [2]基础医学院人体解剖学教研室

出　　处：《第三军医大学学报》2012年第24期2479-2483,共5页Journal of Third Military Medical University

基　　金：国家自然科学基金(30700885);教育部“新世纪优秀人才”支持计划(NCET-11-1084);重庆市首届优秀人才资助计划[渝教人(2009)2号];留学人员科技活动项目择优资助[渝人社办(2011)235号]~~

摘　　要：目的研究γ-分泌酶组件早老素增强子-2(presenilin enhancer-2,Pen-2)在APP/PS1双转基因小鼠脑内的表达及分布,以进一步明确Pen-2与阿尔茨海默病(Alzheimer’s disease,AD)的关系。方法对APP/PS1双转基因小鼠交配后产下的子代进行基因分型,用免疫组化方法检测Pen-2和老年斑在APP/PS1双转基因AD模型小鼠和同窝野生型正常小鼠脑内的分布和表达情况。结果 Pen-2广泛分布于APP/PS1双转基因小鼠脑内各区域,包括大脑皮质、海马、基底核、小脑、嗅脑、脑室脉络丛等,而老年斑则选择性地出现在大脑皮质、海马、嗅脑等区域,并且Pen-2的分布范围广于老年斑的分布。AD模型小鼠大脑新皮质内Pen-2阳性神经元的着色程度(2.09±0.33)显著高于正常小鼠(1.29±0.31,P<0.05),且AD模型小鼠大脑新皮质内Pen-2免疫阳性物质主要分布于细胞膜和细胞质,而正常小鼠大脑新皮质内的Pen-2阳性神经元仅细胞膜周围染色较深,而细胞质染色极浅甚至不着色。结论 Pen-2在AD模型小鼠和正常小鼠脑内的表达存在差异,这种差异可能与老年斑的形成和AD的发生相关。Objective To examine the expression and distribution of presenilin enhancer-2 （Pen-2）, an essential component of γ-secretase complex, in the brain of APP/PS1 double transgenic mice, so as to clarify the relationship between Pen-2 and Alzheimer＇ s disease （AD）. Methods Offspring which were bred by APP/PS1 double transgenic AD mice were genotyped. Immunohistochemical staining was used to check the distribution and expression of Pen-2 in the brain of 8-month-old APP/PS1 double transgenic AD model mice and its age-matched wild-type littermates. Results Pen-2 was widely expressed throughout almost all the regions of brain in APP/PS1 double transgenic mice, including the cerebral cortex, hippocampus, basal nuclei, rhinencephalon, cerebellum, brainstem, and so on. While senile plaques （SP） were selectively distributed in the cerebral cortex, hippocampus, and rhinencephalon. The distribution of Pen-2 was much more extensive than that of SP in the brain of AD model mice. Meanwhile, Pen-2-positive neurons in AD model mice （2.09 ± 0. 33） was more dark-stained than that in wildtype controls （ 1.29 ± 0.31 ） ; Furthermore, both the cell membrane and cytoplasm of Pen-2-positive neurons were heavily stained in the AD mice, while in the wildtype littermates, only membrane and its surrounding of Pen-2-positive neurons were relatively dark-stained, and the cytoplasma was mildly or not stained. Conclusion Distribution and expression of Pen-2 in the brain of APP/ PSI double transgenic mouse model is different from its wildtype littermates. These differences may indicate that Pen-2 is tightly related to SP formation and AD pathogenesis.

关 键 词：Pen-2 γ-分泌酶β淀粉样蛋白 阿尔茨海默病 

分 类 号：R-332[医药卫生] R394.3