爬梯运动提高Presenilin1/Presenilin2双敲鼠的学习记忆能力

Resistance training improves fear learning and memory in presenilin 1 and presenilin 2 double knockout mice

目的 Presenilin1/Presenilin2双基因敲除(PS1/PS2DKO)可导致小鼠学习记忆能力受损,该文主要研究跑台运动和爬梯运动对PS1/PS2 DKO小鼠认知能力的影响,并通过检测运动前后各组小鼠体内神经胶质酸性蛋白(GFAP)、丙二醛(MDA)、超氧化物歧化酶(SOD)等含量的变化,探讨2种运动方式对DKO小鼠认知能力受损的干预效果及其可能的分子机制。方法将6个月龄雄性DKO小鼠及其同窝对照小鼠(CON小鼠)分为4组,分别为CON不运动组、DKO不运动组、DKO跑台组和DKO爬梯组。对DKO跑台组小鼠进行10周的跑台训练,对DKO爬梯组小鼠进行10周的爬梯训练。运动结束后以开场实验、新异物体识别实验和恐惧条件反射实验测试各组小鼠的运动能力和学习记忆能力;用Western blotting、硫代巴比妥酸法、黄嘌呤氧化酶法检测各组小鼠GFAP、MDA、SOD含量的变化。结果爬梯运动可明显改善DKO小鼠的恐惧学习记忆能力;跑台运动和爬梯运动均可降低DKO小鼠前脑中GFAP的含量,但前者也会增加前脑中脂质过氧化程度;而跑台运动和爬梯运动对DKO小鼠前脑中的超氧化物歧化酶活性无明显影响。结论爬梯运动可以改善DKO小鼠的恐惧学习记忆能力,前脑中星型胶质细胞活化程度的降低可能是其分子机制之一。跑台运动对DKO小鼠的学习记忆能力无影响,究其原因可能是跑台运动后DKO小鼠前脑产生大量的氧自由基,其导致的脂质过氧化引起神经细胞损伤,从而抵消了跑台运动对DKO小鼠学习记忆能力的改善作用。

【Objective】 Presenilin 1/ Presenilin 2 double knockout（PS1/PS2DKO） mice displays impaired learning and memory.In our study,we firstly observed the behavioral performance of learning and memory and then evaluated the forebrain expression of GFAP,SOD,MDA in the DKO mice after either aerobic or resistance training,in order to investigate the cognitive influence of different type of physical excises on the DKO mice and shed light on the relative potential mechanism.【Methods】 We divided 6-months-old male mice into 4 groups,CON naive group,DKO naive group,DKO aerobic group,DKO resistance group.After 10 weeks of either aerobic or resistance training,DKO mice were subjected to open field,novel object recognition and fear conditioning tests for the measurement of locomotor activity as well as learning and memory.Western blotting,thiobarbituric acid method and xanthine oxidase assay kit were respectively used to detect the levels of GFAP,SOD and MDA.【Results】 Our data showed that the DKO mice after resistance training had enhancement in the fear learning and memory.GFAP protein expression was reduced in the forebrain of DKO mice after both aerobic and resistance training.Meanwhile,increased lipid peroxidation was found in forebrain of DKO mice after aerobic training.No significant effect was found on the activity of superoxide dismutase in the forebrain between of the DKO mice after aerobic training and of those after resistance training.【Conclusions】 Our findings suggest that the decreased GFAP level in the forebrain of DKO mice may be attributed to the enhanced fear learning and memory in the DKO mice after resistance training.Aerobic training seemed not to facilitate the improvement in fear learning and memory,partly due to the large amounts of oxygen free radicals produced in the brain of DKO mice after aerobic training,which made the neuron damage caused by excessive lipid peroxidation and consequently outweighed the positive effect of aerobic exercise on learning and memory.