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. RT-PCR was applied to test targeted gut microbes. The expression of zonula occludens-۱ (ZO-۱) and Toll-like receptor ۴ (TLR۴)/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 S-۱۰۰β. Additionally, we observed ionized calcium-binding adapter molecule-۱ (Iba-۱) expression in the hippocampal CA۱ 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 ZO-۱ 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 TLR۴/NF-κB 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 TLR۴/NF-kB signaling pathway. The combination of acupoints GV۲۰ and ST۳۶ can enhance the therapeutic effect in aging rats.

Keywords:

Aging Alzheimer’s disease Electroacupuncture Microbiota , Gut , brain axis NF , κB TLR۴