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

目的 研究y-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APH-1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APH-1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、21 d、120 d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1 dAD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、21d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 APH-1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.

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

Objective To investigate the distribution and expression of y-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 transgenic 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 transgenic mouse model and its wild type littermate indicate that APH-1 may be related to AD.