HSP90在APP/PS1小鼠海马组织中年龄依赖性表达变化  

Age-dependent expression of HSP90 in the hippocampus of APP/PS1 mice

作　　者：王冰怡 刘思钰 郝凯敏 祁文秀[1] WANG Bing-Yi;LIU Si-Yu;HAO Kai-Min;QI Wen-Xiu(Fenyang College of Shanxi Medical University,Fenyang 032200,China)

机构地区：[1]山西医科大学汾阳学院,汾阳032200

出　　处：《生理学报》2024年第2期257-265,共9页Acta Physiologica Sinica

基　　金：supported by the Natural Science Foundation of Shanxi Province,China(No.201801D121348);the Scientific Research Project of Fenyang College of Shanxi Medical University,China(No.2022B12)。

摘　　要：本研究旨在观察阿尔茨海默病(Alzheimer’s disease,AD)动物模型海马组织中热休克蛋白90(heat shock protein 90,HSP90)、β-淀粉样蛋白(amyloid-β,Aβ)以及Tau磷酸化水平在不同月龄的变化规律。将6、9、12月龄的APP/PS1转基因小鼠分为3个实验组,同月龄的C57BL/6J小鼠为相应对照组,每组8只。用Morris水迷宫检测各组小鼠的认知行为学能力;Western blot或免疫组织化学检测小鼠海马组织中HSP90、Aβ_(1-42)的表达以及Tau蛋白磷酸化水平;qRT-PCR检测海马组织hsp90 mRNA的表达;尼氏染色检测小鼠海马神经细胞形态和数量的变化。结果显示,APP/PS1转基因小鼠相较于同月龄的C57BL/6J小鼠,其海马组织中HSP90和hsp90 mRNA的表达降低(P<0.05或P<0.01),Aβ_(1-42)和Tau蛋白磷酸化水平则升高(P<0.05或P<0.01);不同月龄的APP/PS1转基因小鼠之间比较后发现,其海马组织中HSP90和hsp90 mRNA表达降低(P<0.05或P<0.01)以及Aβ_(1-42)和Tau蛋白磷酸化水平升高(P<0.01或P<0.05)均随着月龄的增加呈现进行性发展,同时其认知能力也逐渐减退。以上结果提示,APP/PS1小鼠海马组织中HSP90表达降低、Aβ_(1-42)和Tau蛋白磷酸化水平升高及其认知功能降低均呈现年龄依赖性。The present study aims to observe the change in expression of heat shock protein 90(HSP90)along with amyloid-β(Aβ)and phosphorylated Tau(p-Tau)protein levels in the hippocampus tissue of Alzheimer’s disease(AD)transgenic animal model with age.APP/PS1 transgenic mice at age of 6-,9-and 12-month and C57BL/6J mice of the same age were used.The cognitive abilities of these animals were evaluated using a Morris water maze.Western blot or immunohistochemistry was used to detect the expressions of HSP90 and Aβ_(1-42),as well as the phosphorylation levels of Tau protein in the hippocampus.The hsp90 mRNA levels and the morphology and number of cells in the hippocampus were detected with real-time quantitative polymerase chain reaction(qRT-PCR)and Nissl staining,respectively.The results showed that compared with C57BL/6J mice of the same age,HSP90 and hsp90 mRNA expression were decreased(P<0.05 or P<0.01),while Aβ_(1-42) and p-Tau protein levels were increased(P<0.05 or P<0.01)in the hippocampal tissue of APP/PS1 transgenic mice.Meanwhile,the decrease in HSP90 and hsp90 mRNA expression(P<0.05 or P<0.01),the increase in Aβ_(1-42) and p-Tau levels(P<0.01 or P<0.05)in hippocampal tissue and the reduction in behavioral ability showed a progressive development with the advancing of age in the APP/PS1 transgenic mice.In conclusion,in the hippocampal tissue of APP/PS1 mice,the decrease in HSP90 expression and the increase in Aβ_(1-42) and p-Tau levels together with the decline of their cognitive ability are age-dependent.

关 键 词：阿尔茨海默病 HSP90 APP/PS1小鼠 

分 类 号：R749.16[医药卫生—神经病学与精神病学] R-332[医药卫生—临床医学]