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[PTK2B在APPswe/PS1dE9双转基因小鼠海马和血液中的时间依赖性表达谱及其与Aβ、Tau和LRP-1的关系]

[Time dependent expression profiling of PTK2B and its relationship with Aβ, Tau and LRP-1 in hippocampus and blood of APPswe/PS1dE9 double-transgenic mouse].

作者信息

Hao Kai-Min, Liu Zhen, Wang Hao-Yu, Qi Wen-Xiu

机构信息

Fenyang College of Shanxi Medical University, Fenyang 032200, China.

出版信息

Zhongguo Ying Yong Sheng Li Xue Za Zhi. 2022 Jan;38(1):17-24. doi: 10.10247/j.cjap.6191.2022.004.

Abstract

To uncover the time-dependent expression pattern of gene and encoded protein, protein tyrosine kinase 2 beta(PTK2B), in the brain tissues of transgenic animal models of Alzheimer's disease (AD) and its relationship with the levels of Aβ phosphorylation of Tau (p-Tau) and low density lipoprotein receptor-related protein-1(LRP-1) in blood and brain tissues. In this study, 5-, 10- and 15-month-old APPswe/PS1dE9 double-transgenic mice harboring the genotype of AD confirmed by the gene test were divided into the 5-, 10- and 15-month-old experiment groups, and simultaneously, age-matched C57BL/6J mice were placed into the corresponding control groups, with 8 mice in each group. All mice were subjected to the Morris Water Maze for test of cognitive and behavioral ability. Expression profiles of PTK2B, Aβ, p-Tau/Tau and LRP-1 in the hippocampus or blood of mice were quantified by using the immunohistochemistry staining, Western blot or enzyme-linked immunosorbent assay (ELISA), while the mRNA expression of in the hippocampus was quantified by using the real-time quantitative polymerase chain reaction (qRT-PCR). Results of experiment groups demonstrated that as mice aged, the expression levels of PTK2B, mRNA, Aβ and p-Tau/Tau in the hippocampus were increased, and the expression of LRP-1 was decreased gradually. While in the blood, the level of Aβ was decreased, and the cognitive and behavioral ability was decreased in an age-dependent manner (all < 0.05). However, comparisons among the control groups, only the age-dependent downregulation of LRP-1 were observed in hippocampus(<0.05), but other indicators had no significant differences (>0.05). In the hippocampus of APP/PS1 double-transgenic mice, the expressions of PTK2B, Aβ and p-Tau/Tau are upregulated, LRP-1 is downregulated, while cognitive and behavioral ability is decreased, and such changes are presented in a time-dependent manner.

摘要

为揭示基因及编码蛋白蛋白酪氨酸激酶2β(PTK2B)在阿尔茨海默病(AD)转基因动物模型脑组织中的时间依赖性表达模式及其与血液和脑组织中Tau蛋白的β淀粉样蛋白磷酸化(p-Tau)水平和低密度脂蛋白受体相关蛋白1(LRP-1)的关系。本研究将经基因检测确认具有AD基因型的5、10和15月龄APPswe/PS1dE9双转基因小鼠分为5、10和15月龄实验组,同时将年龄匹配的C57BL/6J小鼠放入相应对照组,每组8只。所有小鼠均接受莫里斯水迷宫实验以测试认知和行为能力。采用免疫组织化学染色、蛋白质免疫印迹法或酶联免疫吸附测定(ELISA)对小鼠海马或血液中PTK2B、Aβ、p-Tau/Tau和LRP-1的表达谱进行定量,同时采用实时定量聚合酶链反应(qRT-PCR)对海马中 的mRNA表达进行定量。实验组结果显示,随着小鼠年龄增长,海马中PTK2B、mRNA、Aβ和p-Tau/Tau的表达水平升高,而LRP-1的表达逐渐降低。而在血液中,Aβ水平降低,认知和行为能力呈年龄依赖性下降(均P<0.05)。然而,对照组之间比较,仅在海马中观察到LRP-1随年龄下降(P<0.05),但其他指标无显著差异(P>0.05)。在APP/PS1双转基因小鼠海马中,PTK2B、Aβ和p-Tau/Tau表达上调,LRP-1表达下调,同时认知和行为能力下降,且这些变化呈时间依赖性。

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