Preventive electroacupuncture ameliorates D-galactose-induced Alzheimer’s disease-like inflammation and memory deficits, probably via modulating the microbiota–gut–brain axis

Objective(s): We aimed to observe the effects of preventive electroacupuncture (EA) on the microbiota–gut–brain axis and spatial learning and memory deficits and to investigate the possible mechanism using D-galactose (D-gal)induced aging rats. Materials and Methods: D-gal was intraperitoneally injected to establish the aging model. We used Morris water maze to detect spatial learning and memory function of rats. RTPCR was applied to test targeted gut microbes. The expression of zonula occludens1 (ZO1) and Tolllike receptor 4 (TLR4)/nuclear factor (NF)-κB pathway proteins were detected by Western blotting. ELISA was employed to evaluate the level of lipopolysaccharides (LPS), diamine oxidase (DAO) and S100β. Additionally, we observed ionized calciumbinding adapter molecule1 (Iba1) expression in the hippocampal CA1 area by immunofluorescence. Results: Morris water maze test showed decreased mean escape latency and increased target quadrant time after EA treatment. The gut microbiota composition has been modified in EA treated rats. Molecular examination indicated that expression of ZO1 was improved and the the concentration of LPS in blood and hippocampus were reduced in EA treated rats. Further, we observed an inhibition of activated microglia and TLR4/NFκB pathway in EA groups. Conclusion: Preventive EA may alleviate the impairments of the microbiota–gut–brain axis and spatial learning and memory in aging, and the mechanism may be related to the inhibition of TLR4/NFkB signaling pathway. The combination of acupoints GV20 and ST36 can enhance the therapeutic effect in aging rats.