| 自主运动抑制tau蛋白过度磷酸化改善学习记忆的分子机制 |
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| 引用本文： | 余锋,贾芳芳,徐帅,徐波,张宪亮.自主运动抑制tau蛋白过度磷酸化改善学习记忆的分子机制[J].西安体育学院学报,2021(1):105-115. |
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| 作者姓名： | 余锋 贾芳芳 徐帅 徐波 张宪亮 |
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| 作者单位： | ;1.淮阴师范学院体育学院;2.华东师范大学体育与健康学院;3.山东大学体育学院 |
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| 基金项目： | 江苏省高校自然科学基金(16KJD180001);教育部人文社会科学研究青年基金项目(19YJC890056);国家自然科学基金面上项目(31571225)。 |
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| 摘 要： | 目的探讨自主运动调节tau蛋白激酶和tau蛋白磷酸酶的基因表达,抑制APP/PS1转基因小鼠海马tau蛋白过度磷酸化,进而改善学习记忆能力的分子机制。方法C57系APP/PS1转基因小鼠随机分为运动组(TE)与对照组(TC);C57系野生小鼠亦随机分为运动组(E)与对照组(C)。其中,TE组和E组小鼠从3月龄开始,给予16周的跑轮运动装置,TC组和C组小鼠不施加运动干预,作为相应对照组。Morris水迷宫实验检测APP/PS1转基因小鼠的空间学习记忆能力,Western Blot实验检测海马磷酸化tau蛋白(P-tau)水平,RT-PCR实验检测海马tau蛋白及tau蛋白激酶GSK-3β和CDK-5,tau蛋白磷酸酶PP2A和PP1 mRNA表达。结果(1)与TC组相比,TE组小鼠Morris水迷宫游泳潜伏期显著性降低(P<0.05),平台象限的游泳时间百分比显著性增加(P<0.05),穿越原平台位置的次数极显著性增加(P<0.01);(2)与TC组相比,TE组小鼠海马总tau蛋白mRNA表达显著下调(P<0.05),Ser202位点和Thr181位点P-tau蛋白表达均显著性下调(P<0.05);(3)与TC组相比,TE组小鼠海马tau蛋白磷酸化激酶GSK-3β(P<0.01)和CDK-5(P<0.05)mRNA表达显著性下调,tau蛋白磷酸酶PP2A(P<0.01)和PP1(P<0.01)mRNA表达极显著性下调。结论16周自主运动通过下调tau蛋白激酶表达、上调tau蛋白磷酸酶表达,抑制APP/PS1转基因小鼠海马tau蛋白的过度磷酸化,进而促进海马神经细胞功能,改善转基因小鼠学习记忆。说明自主运动可通过调节脑的分子生物学机制,促进认知功能的改善和提升,预防和缓解阿尔茨海默病。
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| 关 键 词： | 自主运动 阿尔茨海默病 APP/PS1转基因小鼠 海马 TAU蛋白 过度磷酸化 学习记忆 |
Mechanism of Voluntary Exercise Inhibits Hippocampal Tau Hyperphosphorylation Improving Learning and Memory |
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| YU Feng,JIA Fangfang,XU Shuai,XU Bo,ZHANG Xianliang.Mechanism of Voluntary Exercise Inhibits Hippocampal Tau Hyperphosphorylation Improving Learning and Memory[J].Journal of Xi'an Institute of Physical Education,2021(1):105-115. |
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| Authors: | YU Feng JIA Fangfang XU Shuai XU Bo ZHANG Xianliang |
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| Institution: | (Department of Physical Education,Huaiyin Normal University,Huai an 223300,Jiangsu,China;Department of Physical Education&Health,East China Normal University,Shanghai 200241,China;Department of Physical Education,Shandong University,Jinan 250061,China) |
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| Abstract: | Objective To investigate the mechanism of voluntary exercise in inhibiting hippocampal tau hyperphosphorylation,improving learning and memory in APP/PS1 transgenic mice of Alzheimer′s disease(AD).Methods Male APP/PS1 transgenic mice of line C57 that expresses human mutant APP and PS1 in the brain were chosen and divided into wheel running group(TE)and control group(TC).Male wild-type mice in line C57 were chose and divided into wheel running group(E)and control group(C).Mice in group TE and group E were subjected to wheel running with ad libitum access to food and water for 16 weeks from 3 months of age.Mice in group TC and group C were subjected to food and water ad libitum,without exercise.Morris water maze(MWM)was used to examine space learning and memory of mice.Real-time RT-PCR was used to detect mRNA level of tau,GSK-3β,CDK-5,PP2 A and PP1.Western blot was used to detect protein level of phosphorylated-tau(P-tau)at the site of Ser202 and Thr181.Results(1)Compared with group TC,the latency in MWM was significantly decreased,the time percent in platform quadrant was significantly increased(P<0.05)and the crossing times in platform quadrant was very significantly increased(P<0.01)in group TE.(2)Compared with group TC,total mRNA level of tau and protein level of P-tau at the site of Ser202 and Thr181 were all significantly down-regulated(P<0.05)in group TE.(3)Compared with group TC,the mRNA level of GSK-3β(P<0.01)and CDK-5(P<0.05)were significantly down-regulated,the mRNA level of PP2 A(P<0.01)and PP1(P<0.01)were significantly up-regulated in group TE.Conclusion 16 weeks wheel running inhibited tau hyperphosphorylation by inducing the decrease of the phosphorylating enzymes of tau and increased the protein phosphatase of tau dephosphorylation in the hippocampus of APP/PS1 transgenic mice,which promoting the functional recovery of hippocampus neurons and improving learning and memory of APP/PS1 transgenic mice.The resent research indicates that voluntary exercise may promote cognition by regulating the molecular biological mechanism of the brain,preventing and relieving AD. |
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| Keywords: | voluntary exercise Alzheimer′s disease APP/PS1 transgenic mice hippocampus tau hyperphosphorylation learning and memory |
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