Electroacupuncture Ameliorated Locomotor Symptoms in MPTP-Induced Mice Model of Parkinson's Disease by Regulating Autophagy via Nrf2 Signaling

Parkinson's disease (PD) is a prevalent and challenging neurodegenerative disorder, and may involve impaired autophagy. Nuclear factor erythroid-2-related factor 2 (Nrf2) is crucial for regulating autophagy-related genes, maintaining cellular homeostasis. Electroacupuncture (EA), a complementary and alternative therapy for PD, has gained widespread clinical application. In this study, we investigate whether EA at Baihui (GV20) and Taichong (LR3) acupoints modulates autophagy through the Nrf2 pathway, providing neuroprotection in 1 - methyl - 4 - phenyl - 1,2,3,6 - tetrahydropyridine (MPTP) induced PD mice. Using wild-type and Nrf2 knockout (KO) mice, we examined EA's effects on dopaminergic neuron survival, α-synuclein expression, motor function as well as the underlying mechanisms. Results showed that EA treatment significantly reduced dopaminergic neuron loss and α- synuclein expression, and improved motor deficits while restoring autophagy, as evidenced by increased autophagy markers (Atg7, LC3II) and decreased p62 levels. Transmission electron microscopy confirmed a rise in autophagosomes and lysosomes in the MPTP+EA group. EA also enhanced nuclear Nrf2 expression and activated Nrf2 signaling. Importantly, Nrf2 KO mice did not exhibit neuroprotection or increased autophagy-related proteins following EA treatment. In conclusion, our research demonstrated that EA a meliorated defective autophagy and activated the Nrf2 signaling pathway, which collectively contribute to its neuroprotective effects against MPTP-induced neurotoxicity.