Notch1介导有氧运动促进阿尔茨海默病小鼠海马神经细胞的增殖  

Notch1-mediated aerobic exercise promotes hippocampal nerve cell proliferation in Alzheimer’s disease mice

作　　者：李慧军 李垂坤[1] 魏翠兰[2] 张业廷 Li Huijun;Li Chuikun;Wei Cuilan;Zhang Yeting(College of Physical Education,Chengdu University,Chengdu 610106,Sichuan Province,China;Sports Institute of Chengdu University of Technology,Chengdu 610059,Sichuan Province,China;Civil Aviation Flight University of China,Guanghan 618307,Sichuan Province,China)

机构地区：[1]成都大学体育学院,四川省成都市610106 [2]成都理工大学体育学院,四川省成都市610059 [3]中国民用航空飞行学院,四川省广汉市618307

出　　处：《中国组织工程研究》2024年第31期4951-4957,共7页Chinese Journal of Tissue Engineering Research

摘　　要：背景:阿尔茨海默病患者脑部多存在Notch1信号通路异常,但这些信号通路在阿尔茨海默病发病中的作用尚未完全明确。长期有氧运动对于Notch1信号通路的相关因子甲基化率能够产生影响,从而改变Notch1的表达。然而,有氧运动是否会通过Notch1信号通路对阿尔茨海默病小鼠海马神经细胞增殖及组织病理学特征产生影响并不清楚。目的:观察DAPT抑制Notch1信号通路后有氧运动对阿尔茨海默病小鼠海马神经细胞增殖及组织病理学特征的影响。方法:随机将3月龄APP/PS1双转基因阿尔茨海默病小鼠分成4组,分别为对照组、运动对照组、抑制剂组及运动抑制剂组,每组20只。采用自然喂养干预对照组,长期有氧运动干预运动组,各干预方式的周期为20周;然后在第18周对各组小鼠进行溶剂或Notch1抑制剂注射。20周后取脑组织,采用Real-time PCR、免疫荧光及Western blot技术分别检测Aβ1-42、Tau、Ki67及Notch1表达。结果与结论:与对照组小鼠相比,抑制剂组小鼠海马齿状回区Ki67、Notch1的表达显著降低(P<0.05),Aβ1-42、Tau没有显著差异;运动对照组小鼠海马齿状回区Ki67表达显著高于对照组,而Aβ1-42、Tau、Notch1表达显著低于对照组(P<0.05);运动抑制剂组小鼠海马齿状回区Aβ1-42、Tau、Ki67、Notch1表达与抑制剂组相比没有显著差异。由此可见,Notch1信号通路可能介导运动改善阿尔茨海默病小鼠海马神经细胞增殖及组织病理学特征的过程。BACKGROUND:Abnormal Notch1 signaling pathway is mostly found in the brain of Alzheimer’s disease patients,but the role of these signaling pathways in the pathogenesis of Alzheimer’s disease has not been fully clarified.Long-term aerobic exercise can alter the expression of Notch1 by affecting the methylation rate of factors related to the Notch1 signaling pathway.However,it is not clear whether aerobic exercise affects hippocampal nerve cell proliferation and histopathological features of Alzheimer’s disease mice through the Notch1 signaling pathway.OBJECTIVE:To observe the effects of aerobic exercise on the proliferation and histopathological features of hippocampal nerve cells in Alzheimer’s disease mice after DAPT inhibited the Notch1 signaling pathway.METHODS:APP/PS1 double transgenic Alzheimer’s disease mice aged 3 months were randomly divided into four groups:control group,exercise control group,inhibitor group,and exercise inhibitor group,with 20 mice in each group.The control group was fed naturally,and the exercise group received aerobic exercise intervention.Both natural feeding and exercise intervention lasted for 20 weeks.The mice were injected with solvent or Notch1 inhibitor at week 18.After 20 weeks,the brain tissue was collected,and Aβ1-42,Tau,Ki67,and Notch1 expression levels were detected by real-time PCR,immunofluorescence,and western blot assay.RESULTS AND CONCLUSION:Compared with the control group,the expressions of Ki67 and Notch1 in the dentate gyrus region of the hippocampus were significantly decreased in the inhibitor group(P<0.05),but there were no significant differences in Aβ1-42 and Tau.The expression of Ki67 in the dentate gyrus region of the hippocampus in the exercise control group was significantly higher than that in the control group,while the expressions of Aβ1-42,Tau,and Notch1 were significantly lower than those in the control group(P<0.05).The expressions of Aβ1-42,Tau,Ki67,and Notch1 in the dentate gyrus region of the hippocampus of the exercise inhibitor gro

关 键 词：阿尔茨海默病 有氧运动 NOTCH1 神经细胞增殖 

分 类 号：R459.9[医药卫生—治疗学] R319[医药卫生—临床医学] R741.05