Nicastrin在阿尔茨海默病转基因小鼠脑内星形胶质细胞中的表达  

Nicastrin Expression in Brain Astrocytes from Transgenic Alzheimer's Disease Mice

作　　者：邱荣晖[1,2] 林仁[1,2] 赵小贞[1,2] 王玮[1,2] 朱元贵[3] 

机构地区：[1]福建医科大学基础医学院人体解剖与组织胚胎学系,福州350108 [2]福建医科大学神经生物学研究中心,福州350108 [3]福建医科大学附属协和医院老年医学研究所,福州350001

出　　处：《福建医科大学学报》2014年第1期14-18,共5页Journal of Fujian Medical University

基　　金：福建省自然科学基金(201201361)

摘　　要：目的观测阿尔茨海默病(AD)中Nicastrin(NCT)和β-淀粉样蛋白(Aβ)在脑内星形胶质细胞中的表达情况,探讨星形胶质细胞在AD中的病变机制。方法应用荧光免疫组织化学法对5×FAD转基因小鼠海马区染色后,激光共聚焦扫描显微镜观察Nicastrin、Aβ和星形胶质细胞三者位置关系,半定量分析星形胶质细胞、Nicastrin和Aβ的表达变化。结果 (1)野生型小鼠的海马区中未见Nicastrin和Aβ聚积,突变型小鼠海马的第一亚区(CA1)、第三亚区(CA3)、齿状回(DG)中可见Nicastrin和Aβ共定位于星形胶质细胞。(2)荧光半定量结果显示,Nicastrin、Aβ和星形胶质细胞在突变型小鼠的CA1、CA3、DG区的荧光强度均大于野生型小鼠的相应脑区(P<0.05)。(3)体视学计数结果显示,突变型小鼠海马的Aβ、Nicastrin和GFAP的阳性共定位数多于野生型小鼠海马的各相应脑区(P<0.05)。结论 Nicastrin在AD转基因小鼠脑内的星形胶质细胞中表达增多。导致星形胶质细胞损伤的Aβ可能由表达于其中的β-淀粉样前体蛋白切割而成,而非摄取自神经元。Objective To examine the expression of Nicastrin and β-amyloid （Aβ） in brain astrocytes to explore the role of astrocytes in the pathogenesis of Alzheimer＇s disease （AD）. Methods Using immunofluorescence staining the distributions of Nicastrin, Aβ and astrocytes in the hippocampus of 5 × FAD transgenic mice were observed under laser confocal scanning microscope and the changes in expression levels were also semi-quantitated. Results （1） Nicastrin and Aβ were co-localized in astrocytes of the CA1,CA3 and DG in mutant mice but not found in the hippocampus in wild-type mice. （2） Fluorescence semi-quantitative analysis showed that the fluorescence intensity of Nicastrin, Aβ and astrocytes in the DG, CA1, CA3 of mutant mice was higher than that in wild-type mice（P〈0.05）. （3） Stereological counting revealed that the total number of positive colocalization cells with Nicastrin, Aβ and GFAP immunoreactive in mutant mice was greater than that in wild-type mice（P〈0.05）. Conclusion The results indicated that the expression of Nicastrin was significantly increased in the astrocytes of 5 × FAD transgenic mice and At3 that induced the fastrocytic injury may derive from β-amyloid precursor protein rather than neuronal uptake.

关 键 词：阿尔茨海默病 淀粉样Β蛋白 星形细胞 海马 小鼠 转基因 

分 类 号：R749.16[医药卫生—神经病学与精神病学]