摘要
目的:运动锻炼对维持脑功能具有积极的神经生理作用,生理状态下Akt/GSK3激酶信号通路对神经可塑性发挥重要作用,但在病理状态下是否也具有调控作用,为此本研究探讨有氧运动对9月龄AD模型额叶皮层Akt/GSK3信号通路及相关病理变化的影响。方法:以6月龄雄性APP/PS1转基因小鼠为研究对象,随机分为安静组(APP/PS1 Sedentary Group,AS)和运动组(APP/PS1 Exercise Group,AE),同月龄清洁级C57BL/6J小鼠作为安静对照组(C57BL/6J Sedentary Group,CS)和运动对照组(C57BL/6J Exercise Group,CE)。AE与CE组进行为期12周跑台运动。八臂迷宫检测认知行为能力。在最后一次训练48 h后麻醉,取额叶皮层组织进行免疫荧光、免疫组织化学染色及Dot Blot检测Aβ多聚体及低聚物含量,Western Blot检测额叶皮层Akt、GSK3α、GSK3β和Tau蛋白含量及磷酸化修饰水平。结果:12周规律有氧运动可以显著提高9月龄APP/PS1转基因小鼠的行为学表现,降低其额叶皮层Aβ低聚物及多聚体表达(P<0.01),降低Tau蛋白Ser262位点(P<0.05)和Ser396位点磷酸化水平(P<0.05);上调额叶皮层Akt Ser473位点(P<0.01)和GSK3αSer21位点(P<0.01)活性;下调额叶皮层GSK3αTyr279位点(P<0.05)活性;但对额叶皮层GSK3βSer9/GSK3βTyr216位点无影响。结论:12周规律有氧运动通过调节9月龄APP/PS1转基因小鼠额叶皮层Akt/GSK3α信号通路,降低Aβ沉积,减轻病理性Tau蛋白过度磷酸化修饰水平;但该模型较早出现病理改变的额叶皮层GSK3β信号严重受损,长期有氧运动不足以改善额叶皮层GSK3β活性。
Objective:Akt/GSK3 is a neurotrophic-dependent kinase signaling pathway that plays an important role in neural plasticity.Although exercise has a positive neurophysiological effect on maintaining brain function,the possibility of improving brain function under pathological conditions remains unknown.The aim of this study was to investigate the effect of 12 weeks aerobic exercise on AKT/GSK3 signaling pathway and related pathological changes in the frontal area of 9-month-old APP/PS1 transgenic mice.Methods:C57 BL/6 J(6-month-old)and APP/PS1 transgenic mice(6-month-old)were randomly divided into exercise group(CE/AE)and sedentary group(CS/AS)with food and water made available ad libitum,respectively.Animals were subjected to treadmill exercise for 12 weeks from 6 months of age to 9-month old.The changes of behavior were detected by eight-arm radial maze test to evaluate the cognitive function.The expressions of the Aβos,Aβ in the frontal area were detected using Dot Blot,Immunofluorescence technique and Immunohistochemistry.Akt,GSK3α,GSK3β and Tau protein were measured using Western Blot.Results:12 weeks aerobic exercise can enhance behavioral performances of 9-month-old APP/PS1 transgenic mice,decrease the levels of the Aβos and Aβ,increase the activaty of Akt(P<0.05)and pGSK3αser21(P<0.01),and decrease the levels of pTau ser 262(P<0.05)and pTau ser 396(P<0.05)in the frontal area.However,there were no effect on the pGSK3β ser9 and pGSK3β tyr216 in the frontal area.Conclusion:The current findings suggest that the GSK3β signal in the central cortex of APP/PS1 transgenic mice with early pathological changes was severely damaged,and aerobic exercise cannot increase the activity of GSK3β in the central cortex.Aerobic exercise can alleviate the aberrant hyperphosphorylation of Tau protein by regulating the Akt/GSK3αsignaling pathway in the frontal area of 9-month-old APP/PS1 transgenic mice,which is one of the molecular mechanisms for improving brain function and improving spatial learning and memory.
作者
韩鹏
牟连伟
赵丽
HAN Peng;MU Lian-wei;ZHAO Li(School of Sport Science,Beijing Sport University,Beijing 100084,China)
出处
《北京体育大学学报》
CSSCI
北大核心
2021年第1期116-124,共9页
Journal of Beijing Sport University
基金
国家自然科学基金项目“IGF-1/GSK3β通路在有氧运动改善阿尔兹海默病中的作用与机制”(项目编号:31571229)
科技冬奥项目(项目编号:2018YFF0300405)。
