唐氏综合征黏附分子(DSCAM)在APP转基因阳性小鼠小脑内的表达变化及其意义

Expression changes of DSCAM in the cerebellum of APP transgenic mice

目的研究唐氏综合征细胞黏附分子(DSCAM)在β-淀粉样蛋白前体蛋白(APP)转基因小鼠脑内的表达变化规律,初步探讨其意义。方法选择月龄分别为新生、1个月、3个月、6个月和12个月的APP转基因阳性和阴性小鼠,应用免疫组化和免疫荧光法对全脑切片进行染色,观察DSCAM在APP转基因阳性小鼠脑内的表达,特别是在小脑内的表达部位及表达量的变化规律。结果 DSCAM主要在APP转基因阳性模型小鼠小脑中的浦肯野细胞、大脑皮层、海马安蒙氏角(Ammon's horn)的锥体细胞、海马齿状回的颗粒细胞层、丘脑及脑干神经元中表达。新生小鼠和1个月小鼠DSCAM的小脑表达量无明显差异(P>0.05),1月龄小鼠小脑内的表达量较3月龄小鼠低(P<0.05),到达3个月时,其表达量达到高峰,6个月时,DSCAM的表达量和3个月时无明显差异(P>0.05),12月龄的小鼠小脑内的DSCAM的表达量较6月龄低(P<0.05)。在3个月和6个月时,DSCAM在APP转基因阳性小鼠小脑中的表达量明显高于同龄阴性小鼠(P<0.05)。结论 DSCAM在一定月龄APP转基因阳性小鼠小脑内存在过度表达,推测DSCAM作为一种黏附分子,其过度表达在APP小鼠的学习运动能力和运动协调能力的缺陷中可能起重要作用。

[Objective] To investigate the changing regularity of the Down Syndrome Cell Adhesion Molecule （DSCAM） expression in the brain of amyloid precursor protein （APP） transgenic mice and explore the significance of DSCAM expression. [ Methods ] With immunohistochemistry and immumofluorescence, the expression of DSCAM in the brains of APP positive transgenic mice （neonate, aged 1m, 3m, 6m, 12m）, especially the expression pattern of location and strength in cerebellum, was detected. The control groups were APP negative mice （neonate, aged lm, 3m, 6m, 12m）. [Results] We had found that DSCAM widely expressed in the cerebellar purkinje cell, the cerebral cortex, the hippocampal pyramidal cell layer of Ammon＇s horn, the granular layer of the dentate gyms, and the thalamus and brain stem＇s neurons in APP positive transgenic mice. In cerebellum, there wasn＇t a noticeable distinction for the expression of DSCAM in neonatal and 1 month old mice （P 〉0.05）.The expression of DSCAM in the 3rd month old mice was greater than that in the 1st month old mice （P 〈0.05）. There wasn＇t a noticeable difference for the ex- pression of DSCAM in 3rd month and 6th month old mice （P 〉0.05）. At the 12th month, the expression levels began to decrease （P 〈0.05）. For mice of 3 months and 6 months, the expression levels were remarkably higher than those in control groups （P 〈0.05）. [ Conclusions ] At a certain age, DSCAM presents overexpression in the cerebellum of APP positive transgenic mice. As a result, we suppose that DSCAM＇s overexpression may contribute to the defects in the ability of motion and motion coordination as a cell adhesion molecule.