Electroacupuncture Ameliorates Neuroinflammation and Protects Dopaminergic Neurons in Parkinson’s Disease via Gut-Brain Axis Modulation

Objective This study aimed to explore whether the gut - brain axis (GBA) is involved in the protective effect of electroacupuncture (EA) on Parkinson's disease (PD) induced by 6-hydroxydopamine (6-OHDA) injection. Methods Rats of PD model were established by 6-OHDA injection and then divided into four groups: Sham, 6-OHDA, 6-OHDA + EA, and 6-OHDA + MDP (Madopar). The therapeutic effects of EA were observed through behavioral tests, hematoxylin and eosin (H&E) staining, Nissl staining, immunohistochemical staining, and Western blot (WB). Metabolomics methods were used to detect the changes in serum metabolite profiles and short - chain fatty acids (SCFAs). Immunofluorescence staining and WB were employed to observe the regulation of on the balance of regulatory T (Treg) and γδT cells of PD rats. Moreover, the levels of neuroinflammation were detected by quantitative real-time polymerase chain reaction (qPCR) and enzyme-linked immunosorbent assay (ELISA). Results EA significantly ameliorated motor dysfunction in PD rats while preserving neuronal integrity. Metabolomics identified 118 serum metabolites regulated by EA, with restored SCFAs (notably butyrate and propionate). EA enhanced Treg activation and IL-10 expression in the substantia nigra (SN) and colon, inhibited γδT cell activity and IL-17 production, reduced colonic mucosal injury and inflammation, and suppressed systemic and central inflammatory cytokines and their mRNA levels. Conclusion Our findings demonstrated that EA exerted neuroprotective effects in PD rats by ameliorating neuroinflammation, preserving dopaminergic neurons, and enhancing motor function through the modulation of gut-derived metabolites and restoration of Treg/γδT cell balance via the GBA.