γ-分泌酶组件NCT在痴呆小鼠中枢神经系统的分布及表达  

Distribution and expression of γ-secretase subunit nicastrin in central nervous system of Alzheimer′s disease mouse model

作　　者：龙志敏[1] 赵蕾[1] 贺桂琼[2] 宋冲[1] 楚亚楠[1] 

机构地区：[1]重庆医科大学神经科学研究中心,重庆400016 [2]重庆医科大学神经科学研究中心解剖教研室,重庆400016

出　　处：《中国老年学杂志》2011年第11期1999-2003,共5页Chinese Journal of Gerontology

基　　金：国家自然科学基金(No.30700885);教育部重点项目资助计划(No.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(No.KJ090328)

摘　　要：目的研究γ-分泌酶组件蛋白单过性跨膜蛋白(NCT)在APP/PS1双重转基因痴呆小鼠中枢神经系统(CNS)中的分布与表达及与阿尔茨海默病(AD)的关系。方法对APP/PS1双重转基因AD模型种鼠交配后产下的子代进行基因分型,分别用免疫组化、免疫荧光双标及激光共聚焦等技术,检测NCT在APP/PS1双重转基因痴呆小鼠及同窝野生型小鼠CNS内的分布及表达。结果 NCT广泛分布于成年AD小鼠CNS各区域,包括大脑新皮质、海马、嗅脑、丘脑、纹状体、小脑、脑干和脊髓等;而神经元外Aβ的沉积选择性分布于CNS的大脑皮质和海马等区域;大脑皮质及海马内的NCT阳性神经元数量要多于Aβ阳性神经元,且神经元内的Aβ与NCT出现了共存;同时,大脑皮质和海马内的NCT与PS1分布趋势高度一致,且在神经元内出现了共存。痴呆型与同窝野生型新生小鼠大脑皮质内NCT阳性神经元排列致密;随着小鼠的发育,脑组织单位面积内NCT阳性神经元数量逐渐减少;但痴呆小鼠脑内NCT阳性神经元的细胞膜和细胞质均浓染;而同窝野生型小鼠脑内的NCT阳性神经元仅细胞膜周围染色较深,而胞质染色极浅甚至不着色。结论 NCT在痴呆小鼠和正常野生型小鼠脑内的分布及表达出现差异,可能与Aβ的生成和AD的发生相关。Objective To investigate the distribution and expression of γ–secretase subunit nicastrin in central nervous system（CNS） of APP/PS1 double transgenic Alzheimer′s disease（AD） mouse model,so as to further clarify the relationship between NCT and AD.Methods Offspring which were bred by APP/PS1 double transgenic AD mice were genotyped.Various methods such as immunohistochemical staining,double immunofluorescent staining and confocal laser scanning microscope were used to check NCT distribution.Results NCT was widely expressed throughout almost all the regions of CNS（such as cortex,hippocampus,rhinencephalon,hypothalamus,corpus striatum,cerebellum,brainstem and spinal cord） in the adult APP/PS1 double transgenic mice,but extracellular Aβ aggregations（senile plaques） were selectively occured in the limited areas such as cortex,hippocampus.In the cortex and hippocampus of adult AD mouse model,the number of NCT-positive neurons was much more than that of Aβ-positive neurons;Aβ and NCT were colocalized in some neurons.In the brain of adult AD mouse model,the distribution pattern of PS1 was highly similar to that of NCT,and PS1 was co-localized with NCT in the neurons.NCT-positive neurons were distributed in the cortex with highest density in the newborn of AD mouse model and wildtype littermates;with the development of both mice,the number of NCT-positive neurons was gradually decreased per unit area in the cortex.But interestingly,both the cell membrane and cytoplasm of NCT-positive neurons were heavily stained in the AD mouse model at every stage,while in the wildtype littermates,only membrane and its surrounds of NCT-positive neurons were relatively dark-stained,and cytoplasma was less or without stained.Conclusions Distribution and expression of NCT in CNS of APP/PS1 double transgenic mouse model are different from those of its wildtype littermates,indicating that NCT is tightly related to Aβ generation and AD.

关 键 词：单过性跨膜蛋白 Γ-分泌酶 AΒ 中枢神经系统 分布 

分 类 号：R749.1[医药卫生—神经病学与精神病学]