有氧运动调节驱动蛋白改善AD模型皮层线粒体轴突转运

Effects of Aerobic Exercise on Kinesin Improving the Axonal Mitochondrial Transport

目的:观察8周有氧运动对AD小鼠皮层线粒体顺向轴浆转运驱动蛋白的影响。方法:清洁级4月龄APP/PS1、C57BL/6J小鼠各40只随机分为安静组和运动组,运动组进行8周跑台运动,5 d/周,60 min/d,前10 min负荷15 m/min,后50 min负荷18 m/min,坡度为0°。透射电镜观察皮层额叶、颞叶线粒体形态和数目变化;Western blot检测皮层额叶、颞叶线粒体驱动蛋白重链(Kinesin heavy chain,KHC)、驱动蛋白轻链1(Kinesin light chain 1,KLC1)、驱动蛋白轻链2(Kinesin light chain 2,KLC2)表达量。结果:1)电镜下C57正常对照组皮层突触、线粒体结构清晰完整,线粒体数目较多且分布均匀;8周的有氧运动使异常线粒体数目呈减少趋势。电镜下可见安静组APP/PS1小鼠皮层出现神经毡结构松散,少见典型的突触结构,线粒体肿胀、膜破裂,异常线粒体的数目较多;8周的有氧运动改善其突触结构,可见排列整齐的突触小泡增多,异常线粒体数目有所减少。2)安静组APP/PS1组小鼠皮层额叶、颞叶KHC、KLC1、KLC2表达较正常对照组均减少(P<0.05);8周的有氧运动显著提高皮层额叶KHC、KLC1、KLC2和颞叶KHC、KLC1的表达。结论:8周有氧运动可以通过上调APP/PS1小鼠皮层线粒体顺向转运马达蛋白Kinesin重链和轻链的表达,减轻线粒体顺向轴浆转运障碍,增加线粒体在突触的分布,改善突触的结构和功能,是运动改善APP/PS1小鼠行为学的分子机制之一。

Objective： The purpose of this study was to observe the effect of 8 weeks aerobic exercise on anterograde axonal transport of mitochondrial kinesin in the cortex of AD mice. Methods： Forty 4-month old SPF APP / PS1 transgenic mice and C57 BL /6J mice were randomly divided into sedentary（ AS and CS） and exercise groups（ AE and CE） respectively. The exercised groups participated in 8 weeks treadmill exercise at the speed of 15 m / min with 0% slope for 10 min,and 18 m / min for 50 min / d（ 60 min / d）,5 d / week. The mitochondrial morphology and number in the brain tissue were detected by transmission electron microscope. The protein levels of KHC,KLC1,KLC2 were measured by Western blot. Results： 1） In control group,the cortex＇s synapse and the structure of the mitochondria were clear and complete,and the cortex had more mitochondria and their distribution was even. Eight weeks aerobic training alleviated the abnormal mitochondria number. In 6-month-old APP / PS1 mice,the transmission electron showed the neuropil structures in the cortex and hippocampus were loose,the typical synaptic structures were less than the control groups. The swollen mitochondria and ruptured membranes were observed. The number of abnormal mitochondria increased. The 8 weeks aerobic exercise improved the synapse structure,the number of orderly arranged synaptic vesicle increased,and the number of abnormal mitochondria decreased. 2） The expression of KHC,KLC1 and KLC2 in the frontal cortex and temporal lobe of 6 month-old APP / PS1 mice decreased compared with the normal control group（ P〈0. 05）. The 8 weeks aerobic exercise improved the expression of KHC,KLC1 and KLC2 in cortex. Conclusion： The 8 weeks aerobic exercise can mediate the barrier of axoplasmic transport of mitochondria by upregulating the levels of kinesin heavy chain and light chain in APP / PS1 transgenic mice,thereby increasing the distribution of mitochondria in synapse and improving the synaptic structure and function,which may be one of the underlying molecular mechanism of exercise improving behavior learning in mice.