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、Aβ1-42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hsp90mRNA的表达降低(P＜0。05或P＜0。01)，Aβ1-42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Aβ1-42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、Aβ1-42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。
Age-dependent expression of HSP90 in the hippocampus of APP/PS1 mice
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 Aβ1-42,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 Aβ1-42 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 Aβ1-42 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 Aβ1-42 and p-Tau levels together with the decline of their cognitive ability are age-dependent.
Alzheimer's diseaseheat shock protein 90APP/PS1 transgenic mice
王冰怡、刘思钰、郝凯敏、祁文秀
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山西医科大学汾阳学院,汾阳 032200
阿尔茨海默病 HSP90 APP/PS1小鼠
山西省自然科学基金Scientific Research Project of Fenyang College of Shanxi Medical University,China
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