rTMS improves dysphagia by inhibiting NLRP3 inflammasome activation and caspase-1 dependent pyroptosis in PD mice

Abstract

High incidence, severe consequences, unclear mechanism and poor treatment effect are happened in Parkinson's disease-related dysphagia.Repetitive transcranial magnetic stimulation is an effective treatment for dysphagia in Parkinson's disease.However, the therapeutic effect and underlying mechanism of repetitive transcranial magnetic stimulation for dysphagia in Parkinson's disease are still unknown.Neuroinflammation has been proven to be associated with dysphagia in Parkinson's disease, and NLRP3 inflammasome activation and pyroptosis are common neuroinflammatory processes.Therefore, we compared swallowing quality, NLRP3 inflammasome activation, and caspase-1 dependent pyroptosis among NS control, repetitive transcranial magnetic stimulation control, sham repetitive transcranial magnetic stimulation control and L-Dopa control mice by tongue muscle tone detection, immunohistochemistry, immunofluorescence, Western blotting, co-immunoprecipitation and quantitative PCR.The results showed that NLRP3 inflammasome activation and caspase-1 dependent pyroptosis were involved in dysphagia in MPTP-induced Parkinson's disease mice model. Repetitive transcranial magnetic stimulation and L-dopa inhibited the above two pathways to alleviate dopaminergic neuronal damage and improve the quality of dysphagia. Repetitive transcranial magnetic stimulation (1 Hz, 1 time/3 days, 6 weeks) had the same effect on dysphagia as L-dopa treatment (25mg/kg/day, 6 weeks).Finally, we conclude that repetitive transcranial magnetic stimulation will be the preferred option for the treatment of dysphagia in Parkinson's disease in certain conditions such as motor complications secondary to L-Dopa and L-Dopa non-response dysphagia.