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.
J Integr Med. 2024 Sep;22(5):588-599. doi: 10.1016/j.joim.2024.08.002. Epub 2024 Aug 9.
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.
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.
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.
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.
研究表明，电针（EA）通过调节单磷酸腺苷激活的蛋白激酶（AMPK）的表达，可以减轻阿尔茨海默病（AD）引起的认知障碍，但具体机制仍有待阐明。因此，本研究从线粒体动力学的角度探讨了 EA 改善认知功能的潜在机制。
使用 APP/PS1 和 AMPKα1 亚单位条件敲除（AMPKα1-cKO）的 4 月龄转基因小鼠进行实验。为了评估 EA 治疗对认知功能的影响，使用 T 迷宫和 Morris 水迷宫进行评估。此外，还使用化学交换饱和转移、硫黄素染色、透射电子显微镜、线粒体膜电位和 Western blot 检测 EA 对 APP/PS1 小鼠的潜在作用机制。
APP/PS1 小鼠和 AMPKα1-cKO 小鼠均表现出线粒体动力学功能障碍，伴有学习和记忆障碍。AMPK/过氧化物酶体增殖物激活受体-γ 共激活因子-1α（PGC-1α）通路失活增加了病理性淀粉样蛋白-β（Aβ）沉积，并加重了线粒体动力学功能障碍。此外，EA 通过激活 AMPK/PGC-1α 通路，减轻病理性 Aβ 沉积，改善能量代谢，保护线粒体结构和功能，增加线粒体融合蛋白水平，下调分裂蛋白表达，从而挽救 APP/PS1 小鼠的学习和记忆缺陷。然而，AMPKα1 敲除阻碍了 EA 对认知的治疗作用。
调节海马体线粒体动力学和减少 Aβ 沉积通过 AMPK/PGC-1α 通路，对 EA 改善 APP/PS1 小鼠认知障碍的能力至关重要。请引用本文：贾文婉、林慧雯、杨明刚、戴艳琳、丁玉英、徐文帅、王顺年、曹艳君、梁诗鑫、王志福、陈春、刘文利。电针对 APP/PS1 型阿尔茨海默病早期小鼠模型学习记忆的改善作用及其与海马体线粒体动力学的关系。综合医学杂志。2024；22（5）：588-599。
