Electroacupuncture activates AMPKα1 to improve learning and memory in the APP/PS1 mouse model of early Alzheimer's disease by regulating hippocampal mitochondrial dynamics

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外文摘要：Objective:Studies have shown that electroacupuncture(EA)can alleviate cognitive impairments from Alzheimer's disease(AD)by regulating the expression of adenosine monophosphate-activated protein kinase(AMPK),but the specific mechanism involved remains to be elucidated.Therefore,this study explores the potential mechanism by which EA improves cognitive function from the perspective of mito-chondrial dynamics.Methods:The four-month-old transgenic mice with amyloid precursor protein(APP)/presenilin 1(PS1)and AMPKα1-subunit conditional knockout(AMPKα1-cKO)were used for experiments.To evaluate the effects of EA treatment on cognitive function,the T-maze and Morris water maze were used.In addition,chemical exchange saturation transfer,thioflavin staining,transmission electron microscopy,mitochon-drial membrane potential,and Western blotting were used to examine the potential mechanisms under-lying the effects of EA on APP/PS1 mice.Results:Both APP/PS1 mice and AMPKα1-cKO mice exhibited dysfunction in mitochondrial dynamics accompanied by learning and memory impairment.Inactivation of the AMPK/peroxisome proliferator-activated receptor-γ coactivator-1α(PGC-1 α)pathway increased pathological amyloid-β(Aβ)deposition and aggravated the dysfunction in mitochondrial dynamics.In addition,EA rescued learning and memory deficits in APP/PS1 mice by activating the AMPK/PGC-1α pathway,specifically by reducing pathological Aβ deposition,normalizing energy metabolism,protecting the structure and function of mitochondria,increasing the levels of mitochondrial fusion proteins,and downregulating the expression of fission pro-teins.However,the therapeutic effect of EA on cognition in APP/PS1 mice was hindered by AMPKα1 knockout.Conclusion:The regulation of hippocampal mitochondrial dynamics and reduction in Aβ deposition via the AMPK/PGC-1α pathway are critical for the ability of EA to ameliorate cognitive impairment in APP/PS1 mice.

外文关键词：

Adenosine monophosphate-activated protein kinaseAlzheimer's diseaseCognitive impairmentElectroacupunctureHippocampusMitochondrial dynamics

作者：

Wei-wei Jia、Hua-wei Lin、Min-guang Yang、Ya-ling Dai、Yan-yi Ding、Wen-shan Xu、Si-nuo Wang、Ya-jun Cao、Sheng-xiang Liang、Zhi-fu Wang、Cong Chen、Wei-lin Liu

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作者单位：

College of Rehabilitation Medicine,Fujian University of Traditional Chinese Medicine,Fuzhou 350122,Fujian Province,China

The Institute of Rehabilitation Industry,Fujian University of Traditional Chinese Medicine,Fuzhou 350122,Fujian Province,China

National-Local Joint Engineering Research Center of Rehabilitation Medicine Technology,Fujian University of Traditional Chinese Medicine,Fuzhou 350122,Fujian Province,China

Traditional Chinese Medicine Rehabilitation Research Center of State Administration of Traditional Chinese Medicine,Fujian University of Traditional Chinese Medicine,Fuzhou 350122,Fujian Province,China

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出版年：

2024

DOI：

10.1016/j.joim.2024.08.002

结合医学学报(英文版)

上海市中西医结合学会,上海长海医院

结合医学学报(英文版)

CSTPCD

影响因子：0.711

ISSN：2095-4964

年,卷(期)：2024.22(5)