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

Autor: Jia WW; College of Rehabilitation Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, Fujian Province, China., Lin HW; College of Rehabilitation Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, Fujian Province, China., Yang MG; The Institute of Rehabilitation Industry, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, Fujian Province, China., Dai YL; College of Rehabilitation Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, Fujian Province, China., Ding YY; College of Rehabilitation Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, Fujian Province, China., Xu WS; College of Rehabilitation Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, Fujian Province, China., Wang SN; College of Rehabilitation Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, Fujian Province, China., Cao YJ; College of Rehabilitation Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, Fujian Province, China., Liang SX; 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., Wang ZF; 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., Chen C; The Institute of Rehabilitation Industry, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, Fujian Province, China. Electronic address: ccchen2000@163.com., Liu WL; The Institute of Rehabilitation Industry, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, Fujian Province, China. Electronic address: liuweilin12@fjtcm.edu.cn.
Jazyk: angličtina
Zdroj: Journal of integrative medicine [J Integr Med] 2024 Sep; Vol. 22 (5), pp. 588-599. Date of Electronic Publication: 2024 Aug 09.
DOI: 10.1016/j.joim.2024.08.002
Abstrakt: 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-γ coactivator-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-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 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 Aβ deposition via the AMPK/PGC-1α pathway are critical for the ability of EA to ameliorate cognitive impairment in APP/PS1 mice. Please cite this article as: Jia WW, Lin HW, Yang MG, Dai YL, Ding YY, Xu WS, Wang SN, Cao YJ, Liang SX, Wang ZF, Chen C, Liu WL. Electroacupuncture activates AMPKα1 to improve learning and memory in the APP/PS1 mouse model of early Alzheimer's disease by regulating hippocampal mitochondrial dynamics. J Integr Med. 2024; 22(5): 588-599.
(Copyright © 2024 Shanghai Yueyang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine. Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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