Wang Bing-Yi, Liu Si-Yu, Hao Kai-Min, Qi Wen-Xiu
Fenyang College of Shanxi Medical University, Fenyang 032200, China.
Sheng Li Xue Bao. 2024 Apr 25;76(2):257-265.
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, 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 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 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 and p-Tau levels together with the decline of their cognitive ability are age-dependent.
本研究旨在观察阿尔茨海默病(AD)转基因动物模型海马组织中热休克蛋白90(HSP90)表达的变化以及淀粉样β蛋白(Aβ)和磷酸化Tau蛋白(p-Tau)水平随年龄的变化。使用6月龄、9月龄和12月龄的APP/PS1转基因小鼠以及相同年龄的C57BL/6J小鼠。采用Morris水迷宫评估这些动物的认知能力。运用蛋白质免疫印迹法或免疫组织化学法检测海马中HSP90和Aβ的表达以及Tau蛋白的磷酸化水平。分别采用实时定量聚合酶链反应(qRT-PCR)和尼氏染色检测海马中hsp90 mRNA水平以及细胞的形态和数量。结果显示,与相同年龄的C57BL/6J小鼠相比,APP/PS1转基因小鼠海马组织中HSP90和hsp90 mRNA表达降低(P<0.05或P<0.01),而Aβ和p-Tau蛋白水平升高(P<0.05或P<0.01)。同时,APP/PS1转基因小鼠海马组织中HSP90和hsp90 mRNA表达降低(P<0.05或P<0.01)、Aβ和p-Tau水平升高(P<0.01或P<0.05)以及行为能力下降随年龄增长呈进行性发展。综上所述,在APP/PS1小鼠的海马组织中,HSP90表达降低、Aβ和p-Tau水平升高以及认知能力下降均与年龄相关。