摘要
目的研究能量限制对不同年龄小鼠海马mTOR信号通路的影响,并探讨其与认知功能关系。方法将120只C57BL/6小鼠随机分为能量限制组(CR,n=60)和自由摄食组(AL,n=60),CR组摄食量是同龄AL组的70%;分别至1.5、3、12、20月龄(n=15)时,行Morris水迷宫实验后处死取材;采用western blot和免疫组织化学染色法检测海马mTOR通路蛋白表达水平。结果CR抑制各年龄小鼠海马mTOR通路蛋白表达活性(CR vs AL P<0.05或P<0.01);延缓成年后小鼠空间学习功能增龄性退变,体现在逃避潜伏期CR^(20m)<AL^(20m)(P<0.05),穿越平台次数和原平台位置游泳时间CR^(20m)>AL^(20m)(P<0.05);但CR对幼年小鼠学习功能产生不利影响,体现在逃避潜伏期CR^(1.5m)>AL^(1.5m)、CR^(3m)>AL^(3m)(P<0.05),穿越平台次数和原平台位置游泳时间CR^(1.5m)<AL^(1.5m)、CR^(3m)<AL^(3m)(P<0.05)。结论CR对幼年小鼠海马mTOR通路活性的抑制妨碍其认知发育,因此保证充足能量以维持mTOR通路活性对幼年小鼠神经发育至关重要;成年后通过CR抑制mTOR通路可有效延缓认知增龄性退变。
Objective To examine the effects of caloric restriction on mammalian target of rapamycin signaling pathway in hippocampus in mice of different ages and the relationship with the spatial learning capacity.Methods One hundred and twenty C57BL/6 mice were randomly divided into two groups,the caloric restriction(CR)group and ad libitum(AL)group(n=60/group).The CR mice were fed 70%of the food intake by AL mice.At the 1.5,3,12,and 20 months old,respectively(n=15/age group),mice were sacrificed after carrying out the Morris Water Maze test,and the hippocampus were collected properly.Western blot and immunohistochemical analysis were used to test the activity of mTOR signaling pathway.Results CR inhibited the activity of mTOR signaling pathway in the hippocampus(CR vs AL P<0.05,P<0.01).CR postponed age-related decline in hippocampal dependent cognitive function,as indicated by the escape latency with CR^(20m)<AL^(20m)(P<0.05),and the times of crossing the platform and the swimming time at the original platform position with CR^(20m)>AL^(20m)(P<0.05).However,CR had adverse effects on the learning function of young mice,which were reflected in the escape latency with CR^(1.5m)>AL^(1.5m)and CR^(3m)>AL^(3m)(P<0.05),the times of crossing the platform and the swimming time at the original platform position with CR^(1.5m)<AL^(1.5m)and CR^(3m)<AL^(3m)(P<0.05).Conclusion The inhibitory effect of CR on mTOR pathway activity in the hippocampus of young mice hinders their cognitive development.Therefore,sufficient nutrition to maintain mTOR pathway activity is very important for neural development of young mice.Inhibition of mTOR pathway by CR in adults can effectively delay age-related cognitive degeneration.
作者
杨风英
谭思洁
宋祺鹏
傅力
YANG Feng-ying;TAN Si-jie;SONG Qi-peng;FU Li(College of Sports and Health,Shandong Sport University,Jinan 250102;Health Monitoring and Exercise Prescription Research Center,Tianjin Sport University,Tianjin 301617;School of Medical Technology,Tianjin Medical University,Tianjin 300070,China)
出处
《营养学报》
CAS
CSCD
北大核心
2021年第6期538-543,共6页
Acta Nutrimenta Sinica
基金
国家自然科学基金(No.81601962)
全国教育科学规划项目(No.BLA190210)
山东省教育厅青创人才引育计划(No.2019-183)
关键词
能量限制
哺乳动物雷帕霉素靶蛋白
海马
认知
小鼠
caloric restriction
mammalian target of rapamycin
hippocampus
cognition
mouse
作者简介
杨风英(1979-),女,博士,副教授,E-mail:13920960993@163.com;通讯作者:傅力,E-mail:lifu@tmu.edu.cn
