Electroacupuncture alleviates motor dysfunction and gut barrier damage by modulating intestinal NLRP3 inflammasome in MPTP-induced Parkinson's disease mice

Abstract

Abstract Parkinson’s disease (PD) is a neurodegenerative disorder commonly accompanied by motor dysfunction. Electroacupuncture (EA) has shown anti-inflammatory and neuroprotective effects, although the potential mechanisms remain unclear. We speculated that EA could ameliorate the motor dysfunction of PD and that this would be associated with its regulatory impact on the intestinal microbiota. We applied 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to establish a PD mouse model. EA at the GV16, LR3, and ST36 acupoints was administrated for 12 consecutive days. The results of the open-field test indicated that EA alleviated depression and behavioral defects in PD mice. Further study showed that EA upregulated the expressions of tyrosine hydroxylase (TH) and brain-derived neurotrophic factor (BDNF), and blocked the accumulation of α-synuclein (α-syn) in the midbrain. Additionally, EA increased the mRNA levels of neurotrophic factors like BDNF and GDNF. Moreover, EA prevented the damage to intestinal tissues of PD mice, indicative of suppressed NLRP3 inflammasome activation and increased gut barrier integrity. Notably, the antibiotic-treated mouse experiment validated that the gut microbiota was critical in alleviating PD dyskinesia and intestinal inflammation by EA. In conclusion, our study demonstrated that EA intervention could improve PD by alleviating behavioral defects and gut barrier damage, which provides novel insights into the pathogenesis of PD and its therapy.