Affiliation:
1. The Institute of Rehabilitation Industry Fujian University of Traditional Chinese Medicine Fuzhou China
2. Fujian Key Laboratory of Aptamers Technology 900TH hospital of Joint Logistics Support Force Fuzhou China
3. National‐Local Joint Engineering Research Center of Rehabilitation Medicine Technology Fujian University of Traditional Chinese Medicine Fuzhou China
4. Provincial and Ministerial Co‐founded Collaborative Innovation Center of Rehabilitation Technology Fujian University of Traditional Chinese Medicine Fuzhou China
5. Fujian Key Laboratory of Cognitive Rehabilitation Affiliated Rehabilitation Hospital of Fujian University of Traditional Chinese Medicine Fuzhou China
6. Traditional Chinese Medicine Rehabilitation Research Center of State Administration of Traditional Chinese Medicine Fujian University of Traditional Chinese Medicine Fuzhou China
Abstract
AbstractAimsNerve 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.MethodsThe 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.ResultsThe 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 spatial learning memory by reducing Rab5a activity in the early stage of 5 × FAD mice. Moreover, EA could reduce Rab5a activity to increase NGF transduction and increase the levels of phosphorylated TrkA, AKT, and ERK in the basal forebrain and hippocampus, and increase the expression of cholinergic‐related proteins, such as ChAT, vAchT, ChT1, m1AchR, and m2AchR in the basal forebrain and ChAT, m1AchR, and m2AchR in the hippocampus, improving synaptic plasticity in the basal forebrain hippocampal circuit in the early stage of 5 × FAD mice.ConclusionsRab5a hyperactivation is an early pathological manifestation of 5 × FAD mice. EA could suppress Rab5a‐GTP to promote the transduction of NGF signaling, and enhance the synaptic plasticity of the basal forebrain hippocampal circuit improving cognitive impairment in the early stage of 5 × FAD mice.
Funder
National Natural Science Foundation of China
Natural Science Foundation of Fujian Province