Qin Sun1, Ling-Ling Wei2, Min Zhang3, Ting-Xin Li4, Chun Yang5, Shao-Ping Deng2, Qing-Cui Zeng3. 1. a Department of Geratology, Center of Diabetes Mellitus, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, School of Medicine , University of Electronic Science and Technology of China , Chengdu , Sichuan Province , PR China. 2. b Department of Organ Transplantation , Center of Diabetes Mellitus, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China , Chengdu, Sichuan Province , PR China. 3. c Department of Geratology , Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital , Chengdu , PR China. 4. d Department of General Medicine , Health Management Center, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital , Chengdu , PR China. 5. e Department of Gastrointestinal Surgery , Center of Diabetes Mellitus, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu , Chengdu , PR China.
Abstract
BACKGROUND: Type 2 diabetes mellitus (T2DM) is strongly correlated with Alzheimer's disease (AD). Rapamycin has important uses in oncology, cardiology and transplantation medicine. This study aims to investigate effects of rapamycin on AD in hippocampus of T2DM rat by AMPK/mTOR signaling pathway. METHODS: Morris water maze test was applied to evaluate the learning and memory abilities. The fasting plasma glucose (FBG), glycosylated haemoglobin, total cholesterol, triglyceride and serum insulin level were measured. RT-qPCR and Western blot analysis were performed to test expression of AMPK and mTOR. Immunohistochemistry was used to detect the Aβ deposition and immunoblotting to test the total tau, p-tau and Aβ precursor APP expressions. RESULTS: After treated with rapamycin, T2DM rats and rats with T2DM and AD showed increased learning-memory ability, and decreased levels of FBG, glycosylated hemoglobin, total cholesterol, triglyceride and serum insulin, decreased expression of APP and p-tau, increased AMPK mRNA expression and p-AMPK and decreased Aβ deposition, mTOR mRNA expression and p-mTOR. CONCLUSION: The study demonstrated that rapamycin reduces the risk of AD in T2DM rats and inhibits activation of AMPK-mTOR signaling pathway, thereby improving AD lesion in hippocampus of T2DM rats.
BACKGROUND:Type 2 diabetes mellitus (T2DM) is strongly correlated with Alzheimer's disease (AD). Rapamycin has important uses in oncology, cardiology and transplantation medicine. This study aims to investigate effects of rapamycin on AD in hippocampus of T2DM rat by AMPK/mTOR signaling pathway. METHODS: Morris water maze test was applied to evaluate the learning and memory abilities. The fasting plasma glucose (FBG), glycosylated haemoglobin, total cholesterol, triglyceride and serum insulin level were measured. RT-qPCR and Western blot analysis were performed to test expression of AMPK and mTOR. Immunohistochemistry was used to detect the Aβ deposition and immunoblotting to test the total tau, p-tau and Aβ precursor APP expressions. RESULTS: After treated with rapamycin, T2DM rats and rats with T2DM and AD showed increased learning-memory ability, and decreased levels of FBG, glycosylated hemoglobin, total cholesterol, triglyceride and serum insulin, decreased expression of APP and p-tau, increased AMPK mRNA expression and p-AMPK and decreased Aβ deposition, mTOR mRNA expression and p-mTOR. CONCLUSION: The study demonstrated that rapamycin reduces the risk of AD in T2DM rats and inhibits activation of AMPK-mTOR signaling pathway, thereby improving AD lesion in hippocampus of T2DM rats.
Authors: Laura Poupon-Bejuit; Eridan Rocha-Ferreira; Claire Thornton; Henrik Hagberg; Ahad A Rahim Journal: Front Cell Neurosci Date: 2020-05-06 Impact factor: 5.505