p21活化激酶在APP/PS1转基因AD小鼠模型海马内表达的年龄变化(英文)  

Age-related changes of the expression of p21-activated kinase in hippocampus in an APP/PS1 transgenic mice model of Alzheimer’s disease

作　　者：姚君茹[1] 高璐[1] 于剑锋[1] 柴继侠[1] 王月华[1] 马丽香[1] 陈祖林 李瑞锡[1] 彭裕文[1] 

机构地区：[1]复旦大学上海医学院人体解剖与组织胚胎学系,上海200032 [2]洛克菲勒大学神经生物学和遗传学实验室,纽约10021

出　　处：《神经解剖学杂志》2008年第1期1-7,共7页Chinese Journal of Neuroanatomy

摘　　要：阿尔茨海默病(Alzheimer's disease,AD)与突触障碍密切相关,p21活化激酶(p21-activated kinase,PAK)在突触功能调节中起重要作用。然而,PAK与AD病理学变化之间的关系,尚不清楚。本实验用分子生物学及组织化学等方法检测了不同周龄APP/PS1转基因AD小鼠模型海马中PAK3(PAK的代表性亚型)、pPAK(磷酸化的PAK)和Aβ42(含42个氨基酸片断的Aβ多肽)的表达水平以及神经元的形态学变化。Western Blot结果显示,海马中PAK3的表达,在不同年龄的APP/PS1转基因AD模型小鼠和非转基因小鼠中,均没有显著性差别;而pPAK表达则出现显著性降低(32周),并且随年龄增长进一步下降。Aβ42的水平在转基因AD小鼠模型海马中增加较早(22周),并随年龄的增长而显著增加。Nissl染色显示,转基因AD小鼠模型海马神经元无明显数量变化;而Golgi银染法显示,转基因AD小鼠模型海马神经元的树突显著变形、紊乱。这些结果说明,在APP/PS1转基因AD小鼠模型PAK表达正常,但PAK的磷酸化过程出现了异常,导致其活性不足。Aβ42的毒性作用可能是导致pPAK活性下降的原因,而pPAK的下降又可能是影响海马神经元树突发育、造成其变形、紊乱的直接原因。It has been known that the Alzheimer＇s disease （AD） is related closely with a synaptic failure, and the p21-activated kinase （PAK） is well documented to play an important role in the regulation of the synaptic functions. However, the relationship between the PAK and the pathology of AD is unclear. In the present study, we examined the expressions of the PAK3 （one subtype of PAK）, phosphorylated-PAK （pPAK） and β-amyloid42 （Aβ42, β-amyloid with 42 peptides） in an APP/PSI double transgenic mouse model of AD and the morphologies of neurons in the hippocampus at different ages. The Western Blot results showed that the expression of PAK remained unchanged, while, the expression of pPAK decreased largely at the age of 32 weeks and further decreased significantly with aging in the hippocampus of the APP/PSI transgenic mouse. Aβ42 levels in the hippocampus were detected to increase as early as the age of 22 weeks, and kept the increase to continue with aging. The morphological results showed no obvious neuron loss in the sections of Nissl staining, while serious distortion and disorder of the dendrites of the hippocampal neurons were observed on the sections of Golgi staining in the APP/PSI transgenie mouse. The present results suggested that it seemed something wrong in the processes of phospholization of PAK, but not in the expression of the PAK itself; the toxic Aβ42 might affect the PAK in its phospholization, which in turn directly influence the dendritic development in the hippocampal neurons and cause the dendrites distorting and disordering.

关 键 词：P21活化激酶 AΒ42 树突 海马 APP/PS1转基因小鼠 阿尔茨海默病 

分 类 号：R749.16[医药卫生—神经病学与精神病学]