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目的:探讨DNA甲基化在运动缓解阿尔茨海默病中的作用。方法:选3月龄APP/PS1转基因小鼠24只,随机分为转基因运动组(TE,n=12)和转基因对照组(TC,n=12),选同系野生型小鼠作为正常对照组(C,n=12)和运动对照组(E,n=12)。E组和TE组给予10周的跑台运动,C组和TC组安静饲养。运动结束后Morris水迷宫检测小鼠学习记忆能力,水迷宫试验后取海马组织,RT-PCR法检测小鼠海马甲基化转移酶DNMT1、DNMT3a、DNMT3b m RNA表达水平,Western Blot检测小鼠海马APP、PS1、Aβ42蛋白表达情况。结果:与C组相比,TC组小鼠海马DNMT1m RNA表达水平显著降低(P<0.01),DNMT3a m RNA表达水平显著降低(P<0.05),DNMT3b m RNA表达水平显著降低(P<0.05),APP蛋白表达水平显著增加(P<0.01),PS1蛋白表达水平显著增加(P<0.01),Aβ42蛋白表达水平显著增加(P<0.01),学习记忆能力显著降低(P<0.05)。与TC组相比,TE组小鼠海马DNMT1m RNA表达水平显著增加(P<0.05),DNMT3a m RNA表达水平显著增加(P<0.05),DNMT3b m RNA表达水平显著增加(P<0.05),APP蛋白表达水平显著降低(P<0.05),PS1蛋白表达水平显著降低(P<0.05),Aβ42蛋白表达水平显著降低(P<0.05),空间记忆能力显著增强(P<0.05)。结论:10周的跑台运动通过增加AD小鼠海马DNMT表达水平,提高海马DNA甲基化水平,抑制APP、PS1蛋白表达,减少Aβ42的生成,提高AD小鼠的学习记忆能力。
Abstract：This experiment is to investigate the effect and mechanism of DNA methylation on exercise which can alleviate Alzheimer's disease. Methods: 3months old APP/PS1 transgenic mice were divided into transgenic exercise group(TE,n=12)and transgenic control group(TC,n=12)randomly. Wild typemice were chose as normal control group(C,n=12)and exercise group(E,n=12). Group E and group TE was given 10 weeks treadmill,group C and group TCwere sec. Morris water maze test mice space memory ability after 10 weeks exercise,all mice were killed to obtain hippocampus,gene expression of DNMT1,DNMT3 a and DNMT3 b was detected by real time RT-PCR,protein expression levels of APP,PS1 and Aβ42 in mice hippocampus was detected by WesternBlot. Results: Compared with group C,m RNA expression level of DNMT1 was significantly lower in TC group(P<0.01),m RNA expression level of DNMT3 awas significantly lower in TC group(P<0.05),m RNA expression level of DNMT3 b was significantly lower in TC group(P<0.05),protein expression level ofAPP was significantly higher(P<0.01),protein expression level of PS1 was significantly higher(P<0.01),protein expression level of Aβ42was significantlyhigher(P<0.01),spatial memory ability was significantly lower than normal control group(P<0.05). compared with group TC,m RNA expression level of DN-MT1 was significantly higher(P<0.05),m RNA expression level of DNMT3 a was significantly higher(P<0.05),m RNA expression level of DNMT3 b was signif-icantly higher(P<0.05),protein expression level of APP was significantly lower in TE group(P<0.05),protein expression level of PS1 was significantly lowerin TE group(P<0.05),protein expression level of Aβ42 was significantly lower in TE group(P<0.05),spatial memory ability is significantly higher in TEgroup compare to TC group(P<0.05). Conclusions: 10 weeks treadmill increased DNMT expression level and DNA methylation level in AD mice hippocampus.It also inhibited APP and PS1 protein expression level,reducing Aβ42 generation and finally improve AD mice spatial learning and memory ability.
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基本信息:
DOI：10.13297/j.cnki.issn1005-0000.2016.04.011
中图分类号:R749.16
引用信息:
[1]何标,徐波,张宪亮.运动通过提高DNA甲基化水平改善阿尔茨海默病小鼠空间学习记忆能力[J].天津体育学院学报,2016,31(04):333-339.DOI:10.13297/j.cnki.issn1005-0000.2016.04.011.
基金信息:
国家自然科学基金项目(项目编号:31571225)