PMID- 32375443 OWN - NLM STAT- MEDLINE DCOM- 20200717 LR - 20211204 IS - 0376-2491 (Print) IS - 0376-2491 (Linking) VI - 100 IP - 17 DP - 2020 May 5 TI - [Effect of mammalian target of rapamycin on cognitive dysfunction of Alzheimer's Disease via regulating Homer3]. PG - 1336-1340 LID - 10.3760/cma.j.cn112137-20191108-02437 [doi] AB - Objective: To exploer the effect of mammalian target ofrapamycin(mTOR)on cognitive dysfunction of mice with Alzheimer's disease (AD) induced by amyloid beta(1-42) (Abeta(1-42)) via observing the regulation effect of rapamycin on Homer3 in hippocampus. Methods: The 32 mice were randomly divided into fourgroups: sham group (the hippocampus of mice was injected with normal saline); AD group (the hippocampus of mice was injected with Abeta(1-42)); DMSO group(AD mice induced by Abeta(1-42) were intraperitoneally injected with dimethylsulfoxide for 14 days);RAPA group(AD mice induced by Abeta(1-42) were intraperitoneally injected with rapamycin 1 mg/kg for 14 days). Morris maze and Y maze experiments to measuring cognitive function and immunowestern bloting detecting the expression of Abeta(1-42), mTOR, p-mTOR and Homer3 in the hippocampus were conducted on each group of mice. Results: Compared with sham group,the AD group showed significantly longer escape latency,shoter residence time of objective quadrant, less numbers of crossing of original platform, lower alternation ratio(P<0.05); Compared with DMSO group, RAPA group showed significantly shorter escape latency, longer residence time of objective quadrant, more numbers of crossing of original platform, more alternation ratio(P<0.05). The levels of Abeta(1-42) and p-mTOR were increased, the levels of Homer3 were decreased in DMSO group mice's hippocampus compared with sham group(P<0.05); the levels of Abeta(1-42) and p-mTOR were decreased,the levels of Homer3 were increased in RAPA group mice's hippocampus compared with DMSO group(P<0.05). Conclusion: The inhibitor of mTOR rapamycin can improve the cognitive dysfunction of mice with AD induced by Abeta(1-42) and reduce deposition of Abeta(1-42) in the hippocampus, and the possible mechanism is rapamycin depressing the phosphorylation of mTOR as the same as Up-regulation the expression level of Homer3. FAU - Huang, Y Q AU - Huang YQ AD - Department of Anesthesiology, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine,Hangzhou 310006,China. FAU - Liu, X G AU - Liu XG AD - Department of Anesthesiology, the Second Affiliated Hospital of Wenzhou Medical University, Wenzhou 325027, China. FAU - Zhang, L AU - Zhang L AD - the Fourth Clinical College of Zhejiang Chinese Medical University, Hangzhou 310053, China. FAU - Yu, Y AU - Yu Y AD - the Fourth Clinical College of Zhejiang Chinese Medical University, Hangzhou 310053, China. FAU - Xue, J AU - Xue J AD - the Fourth Clinical College of Zhejiang Chinese Medical University, Hangzhou 310053, China. FAU - Sun, J L AU - Sun JL AD - Department of Anesthesiology, the Second Affiliated Hospital of Wenzhou Medical University, Wenzhou 325027, China. LA - chi GR - LY17C090002/Zhejiang Provincial Natural Science Foundation/ GR - 20170533B32/Social Development Project of Hangzhou Science And Technology Commission/ GR - 2017KY520/Medical Health Research Program of Zhejiang Province/ PT - Journal Article PL - China TA - Zhonghua Yi Xue Za Zhi JT - Zhonghua yi xue za zhi JID - 7511141 RN - 0 (Amyloid beta-Peptides) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) RN - W36ZG6FT64 (Sirolimus) SB - IM MH - *Alzheimer Disease MH - Amyloid beta-Peptides MH - Animals MH - *Cognitive Dysfunction MH - Disease Models, Animal MH - Hippocampus MH - Mice MH - Sirolimus MH - TOR Serine-Threonine Kinases OTO - NOTNLM OT - Alzheimer's disease OT - Amyloid beta(1-42) OT - Mammalian target ofrapamycin OT - Phosphorylate-mammalian target of rapamycin OT - Rapamycin EDAT- 2020/05/08 06:00 MHDA- 2020/07/18 06:00 CRDT- 2020/05/08 06:00 PHST- 2020/05/08 06:00 [entrez] PHST- 2020/05/08 06:00 [pubmed] PHST- 2020/07/18 06:00 [medline] AID - 10.3760/cma.j.cn112137-20191108-02437 [doi] PST - ppublish SO - Zhonghua Yi Xue Za Zhi. 2020 May 5;100(17):1336-1340. doi: 10.3760/cma.j.cn112137-20191108-02437.