CAJ | 학술논문

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的代表性哑型)、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Gelgi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.
아이자해묵병(Alzheimer's disease,AD)여돌촉장애밀절상관,p21활화격매(p21-activated kinase,PAK)재돌촉공능조절중기중요작용.연이,PAK여AD병이학변화지간적관계,상불청초.본실험용분자생물학급조직화학등방법검측료불동주령APP/PS1전기인AD소서모형해마중PAK3(PAK적대표성아형)、pPAK(린산화적PAK)화Aβ42(함42개안기산편단적Aβ다태)적표체수평이급신경원적형태학변화.Western Blot결과현시,해마중PAK3적표체,재불동년령적APP/PS1전기인AD모형소서화비전기인소서중,균몰유현저성차별;이pPAK표체칙출현현저성강저(32주),병차수년령증장진일보하강.Aβ42적수평재전기인AD소서모형해마중증가교조(22주),병수년령적증장이현저증가.Nissl염색현시,전기인AD소서모형해마신경원무명현수량변화;이Gelgi은염법현시,전기인AD소서모형해마신경원적수돌현저변형、문란.저사결과설명,재APP/PS1전기인AD소서모형PAK표체정상,단PAK적린산화과정출현료이상,도치기활성불족.Aβ42적독성작용가능시도치pPAK활성하강적원인,이pPAK적하강우가능시영향해마신경원수돌발육、조성기변형、문란적직접원인.
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 synaptie functions.However,the relationship between thePAK and the pathology of AD is unclear.In the present study,we examined the expressions of the PAK3(one subtype ofPAK),phospho-rylated-PAK(pPAK) and β-amyloid42(Aβ42,β-amyloid with 42 peptides)in an APP/PS1 double transgenie mouse model of AD andthe morphologies of geurOtlS in the hippocampus at different ages.The Western Blot results showed that the expression of PAK remainedunchanged,while,the expression of pPAK decreased largely at the age of 32 weeks and further decreased significantly with aging in thehippocampus of the APP/PS1 transgenic mouse.A1342 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 distonion and disorder of the dendrites of the hippocampal neurons were observed on the sections of Gelgi staining in theAPP/PS1 transgenic mouse.The present results suggested that it seemed something wrong in the processes of phospholization of PAK,butnot in the expression of the PAK itself;the toxic Aβ42 might affect the PAK in its phospholization,which in turn directly influence thedendritic development in the hippocampal neurons and cause the dendrites distorting and disordering.