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

机构地区：[1]College of Rehabilitation Medicine,Fujian University of Traditional Chinese Medicine,Fuzhou 350122,Fujian Province,China [2]The Institute of Rehabilitation Industry,Fujian University of Traditional Chinese Medicine,Fuzhou 350122,Fujian Province,China [3]National-Local Joint Engineering Research Center of Rehabilitation Medicine Technology,Fujian University of Traditional Chinese Medicine,Fuzhou 350122,Fujian Province,China [4]Traditional Chinese Medicine Rehabilitation Research Center of State Administration of Traditional Chinese Medicine,Fujian University of Traditional Chinese Medicine,Fuzhou 350122,Fujian Province,China

出　　处：《Journal of Integrative Medicine》2024年第5期588-599,共12页结合医学学报（英文版）

基　　金：supported by the Fujian Provincial Outstanding Natural Science Foundation(No.2021J06028);the key project at the central government level:the ability establishment of sustainable use for valuable Chinese Medicine Resources(No.2060302).

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 mitochondrial 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,mitochondrial membrane potential,and Western blotting were used to examine the potential mechanisms underlying 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-γcoactivator-1α(PGC-1α)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-1αpathway,specifically by reducing pathological Aβdeposition,normalizing energy metabolism,protecting the structure and function of mitochondria,increasing the levels of mitochondrial fusion proteins,and downregulating the expression of fission proteins.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 Aβdeposition via the AMPK/PGC-1αpathway are critical for the ability of EA to ameliorate cognitive impairment in APP/PS1 mice.

关 键 词：Adenosine monophosphate-activated protein kinase Alzheimer’s disease Cognitive impairment ELECTROACUPUNCTURE HIPPOCAMPUS Mitochondrial dynamics 

分 类 号：R245[医药卫生—针灸推拿学]