Electroacupuncture Inhibits the Early Neuroinflammatory Cascade Triggered by TLR2 in the Prodromal Period of PD

Objective: To explore electroacupuncture (EA)'s effect and mechanism in alleviating prodromal Parkinson's disease (pPD) by targeting TLR2-mediated neuroinflammation. Methods: Rat pPD models were established via striatal 10 μg/4 μL 6-OHDA injection. EA was applied at DU20, EX-HN3, LR2, and LR3 for 14 days. Behavioral tests, ELISA, immunohistochemistry, immunofluorescence, Western blot and qRT-PCR were used to assess non-motor symptoms, DA/TH levels, TLR2 expression, microglial activation, TLR2/NF-κB/NLRP3 pathway and pyroptosis. Results: 6-OHDA induced 30-40% striatal DA reduction and typical pPD non-motor symptoms. EA significantly improved these symptoms, reduced TLR2 expression in key regions (substantia nigra, hippocampus, etc), inhibited M1 microglial activation (decreased CD86, increased CD206), and suppressed TLR2/NF-κB/NLRP3 pathway-related proteins, and inhibits microglial pyroptosis. Conclusion: EA inhibited the neuroinflammation and microglial cell activation as well as pyroptosis mediated by TLR2, thereby alleviating the non-motor symptoms of PD. This provides a potential possibility for the intervention treatment of PD to prevent the progression of the disease.