Electroacupuncture regulates Rab5a‐mediating NGF transduction to improve learning and memory ability in the early stage of AD mice

作者：Jianhong Li, Minguang Yang, Yaling Dai, Xiaoqin Guo, Yanyi Ding, Xiaoling Li, Shenghang Zhang, Wenshan Xu, Lidian Chen, Jing Tao, Weilin Liu · 发表于：CNS Neuroscience & Therapeutics · 年份：2024 · DOI：10.1111/cns.14743 · 被引用次数：9 · 研究领域：Alzheimer's disease research and treatments、Acupuncture Treatment Research Studies、Neuroscience and Neuropharmacology Research

AIMS: Nerve growth factor (NGF) loss is a potential factor for the degeneration of basal forebrain cholinergic neurons (BFCNs) in Alzheimer's disease (AD), and Rab5a is a key regulatory molecule of NGF signaling transduction. Here, we investigated the changes of Rab5a in 5 × FAD mice and further explored the mechanism of Electroacupuncture (EA) treatment in improving cognition in the early stage of AD. METHODS: The total Rab5a and Rab5a-GTP in 5-month-old 5 × FAD mice and wild-type mice were detected using WB and IP technologies. 5 × FAD mice were treated with EA at the Bai hui (DU20) and Shen ting (DU24) acupoints for 4 weeks and CRE/LOXP technology was used to confirm the role of Rab5a in AD mediated by EA stimulation. The Novel Object Recognition and Morris water maze tests were used to evaluate the cognitive function of 5 × FAD mice. The Nissl, immunohistochemistry, and Thioflavin S staining were used to observe pathological morphological changes in the basal forebrain circuit. The Golgi staining was used to investigate the synaptic plasticity of the basal forebrain circuit and WB technology was used to detect the expression levels of cholinergic-related and NGF signal-related proteins. RESULTS: The total Rab5a was unaltered, but Rab5a-GTP increased and the rab5a-positive early endosomes appeared enlarged in the hippocampus of 5 × FAD mice. Notably, EA reduced Rab5a-GTP in the hippocampus in the early stage of 5 × FAD mice. EA could improve object recognition memory and s...