Electroacupuncture Protects Cognition by Regulating Tau Phosphorylation and Glucose Metabolism via the AKT/GSK3β Signaling Pathway in Alzheimer’s Disease Model Mice
BackgroundAlzheimer’s disease (AD) is mainly manifested as a continuous and progressive decline in cognitive ability. Neurofibrillary tangles (NFTs) are pathological hallmarks of AD and due to accumulated phosphorylated Tau. Glycogen synthase kinase-3β (GSK3β), as a major Tau kinase and a downstream...
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doaj-fdea0f1e47f044d9ba8ce313514d51532020-11-25T04:03:29ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2020-11-011410.3389/fnins.2020.585476585476Electroacupuncture Protects Cognition by Regulating Tau Phosphorylation and Glucose Metabolism via the AKT/GSK3β Signaling Pathway in Alzheimer’s Disease Model MiceAnping Xu0Qingtao Zeng1Yinshan Tang2Xin Wang3Xiaochen Yuan4You Zhou5Zhigang Li6School of Acupuncture-moxibustion and Tuina, Beijing University of Chinese Medicine, Beijing, ChinaInformation Engineering Institute, Beijing Institute of Graphic Communication, Beijing, ChinaDepartment of Rehabilitation and Traditional Chinese Medicine, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, ChinaBeijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, ChinaKey Laboratory of Microcirculation, Ministry of Health, Institute of Microcirculation, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, ChinaDepartment of Rehabilitation and Traditional Chinese Medicine, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, ChinaSchool of Acupuncture-moxibustion and Tuina, Beijing University of Chinese Medicine, Beijing, ChinaBackgroundAlzheimer’s disease (AD) is mainly manifested as a continuous and progressive decline in cognitive ability. Neurofibrillary tangles (NFTs) are pathological hallmarks of AD and due to accumulated phosphorylated Tau. Glycogen synthase kinase-3β (GSK3β), as a major Tau kinase and a downstream target of the serine protein kinase B (AKT) signaling pathway, can regulate Tau phosphorylation in AD. Importantly, the AKT/GSK3β signaling pathway is involved in glucose metabolism, and abnormal glucose metabolism is found in the AD brain. Numerous studies have shown that electroacupuncture (EA), which is thought to be a potential complementary therapeutic approach for AD, can protect cognitive ability to a certain extent.ObjectiveThe purpose of this experiment was to investigate whether the protective and beneficial mechanism of EA on cognition was mediated by the AKT/GSK3β signaling pathway, thereby improving glucose metabolism and Tau phosphorylation in the brain.MethodsEA was applied to the Baihui (GV20) and Yintang (GV29) acupoints of 6-month-old amyloid precursor protein (APP)/presenilin-1 (PS1) mice for 20 min, and then quickly prick Shuigou (GV26) acupoint. The intervention was performed once every other day for 28 days. The Morris water maze (MWM) test was performed on C57BL/6N (Non-Tg) mice, APP/PS1 (Tg) mice and EA-treated Tg (Tg + EA) mice to evaluate the effect of EA therapy on cognitive function. 18F-FDG positron emission tomography (PET), immunohistochemistry, and western blotting (WB) were used to investigate the possible mechanism underlying the effect of EA on AD.ResultsEA treatment significantly improved the cognition of APP/PS1 mice and the glucose uptake rate in the hippocampus. Furthermore, EA inhibited the phosphorylation of Tau (Ser199 and Ser202) proteins by inducing AKT (Ser473) and GSK3β (Ser9) phosphorylation.ConclusionThese results demonstrate that EA intervention protects cognition by enhancing glucose metabolism and inhibiting abnormal phosphorylation of Tau protein in the AD model mice, and the AKT/GSK3β pathway might play an irreplaceable role in the regulation process.https://www.frontiersin.org/articles/10.3389/fnins.2020.585476/fullAlzheimer’s diseaseelectroacupucnturecognitionglucose metabolismtauAKT/GSK3β pathway |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Anping Xu Qingtao Zeng Yinshan Tang Xin Wang Xiaochen Yuan You Zhou Zhigang Li |
spellingShingle |
Anping Xu Qingtao Zeng Yinshan Tang Xin Wang Xiaochen Yuan You Zhou Zhigang Li Electroacupuncture Protects Cognition by Regulating Tau Phosphorylation and Glucose Metabolism via the AKT/GSK3β Signaling Pathway in Alzheimer’s Disease Model Mice Frontiers in Neuroscience Alzheimer’s disease electroacupucnture cognition glucose metabolism tau AKT/GSK3β pathway |
author_facet |
Anping Xu Qingtao Zeng Yinshan Tang Xin Wang Xiaochen Yuan You Zhou Zhigang Li |
author_sort |
Anping Xu |
title |
Electroacupuncture Protects Cognition by Regulating Tau Phosphorylation and Glucose Metabolism via the AKT/GSK3β Signaling Pathway in Alzheimer’s Disease Model Mice |
title_short |
Electroacupuncture Protects Cognition by Regulating Tau Phosphorylation and Glucose Metabolism via the AKT/GSK3β Signaling Pathway in Alzheimer’s Disease Model Mice |
title_full |
Electroacupuncture Protects Cognition by Regulating Tau Phosphorylation and Glucose Metabolism via the AKT/GSK3β Signaling Pathway in Alzheimer’s Disease Model Mice |
title_fullStr |
Electroacupuncture Protects Cognition by Regulating Tau Phosphorylation and Glucose Metabolism via the AKT/GSK3β Signaling Pathway in Alzheimer’s Disease Model Mice |
title_full_unstemmed |
Electroacupuncture Protects Cognition by Regulating Tau Phosphorylation and Glucose Metabolism via the AKT/GSK3β Signaling Pathway in Alzheimer’s Disease Model Mice |
title_sort |
electroacupuncture protects cognition by regulating tau phosphorylation and glucose metabolism via the akt/gsk3β signaling pathway in alzheimer’s disease model mice |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Neuroscience |
issn |
1662-453X |
publishDate |
2020-11-01 |
description |
BackgroundAlzheimer’s disease (AD) is mainly manifested as a continuous and progressive decline in cognitive ability. Neurofibrillary tangles (NFTs) are pathological hallmarks of AD and due to accumulated phosphorylated Tau. Glycogen synthase kinase-3β (GSK3β), as a major Tau kinase and a downstream target of the serine protein kinase B (AKT) signaling pathway, can regulate Tau phosphorylation in AD. Importantly, the AKT/GSK3β signaling pathway is involved in glucose metabolism, and abnormal glucose metabolism is found in the AD brain. Numerous studies have shown that electroacupuncture (EA), which is thought to be a potential complementary therapeutic approach for AD, can protect cognitive ability to a certain extent.ObjectiveThe purpose of this experiment was to investigate whether the protective and beneficial mechanism of EA on cognition was mediated by the AKT/GSK3β signaling pathway, thereby improving glucose metabolism and Tau phosphorylation in the brain.MethodsEA was applied to the Baihui (GV20) and Yintang (GV29) acupoints of 6-month-old amyloid precursor protein (APP)/presenilin-1 (PS1) mice for 20 min, and then quickly prick Shuigou (GV26) acupoint. The intervention was performed once every other day for 28 days. The Morris water maze (MWM) test was performed on C57BL/6N (Non-Tg) mice, APP/PS1 (Tg) mice and EA-treated Tg (Tg + EA) mice to evaluate the effect of EA therapy on cognitive function. 18F-FDG positron emission tomography (PET), immunohistochemistry, and western blotting (WB) were used to investigate the possible mechanism underlying the effect of EA on AD.ResultsEA treatment significantly improved the cognition of APP/PS1 mice and the glucose uptake rate in the hippocampus. Furthermore, EA inhibited the phosphorylation of Tau (Ser199 and Ser202) proteins by inducing AKT (Ser473) and GSK3β (Ser9) phosphorylation.ConclusionThese results demonstrate that EA intervention protects cognition by enhancing glucose metabolism and inhibiting abnormal phosphorylation of Tau protein in the AD model mice, and the AKT/GSK3β pathway might play an irreplaceable role in the regulation process. |
topic |
Alzheimer’s disease electroacupucnture cognition glucose metabolism tau AKT/GSK3β pathway |
url |
https://www.frontiersin.org/articles/10.3389/fnins.2020.585476/full |
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