Impaired brain-gut circuit for gut motility dysfunction in mouse models of Parkinson's disease

Gut motility dysfunction is a common symptom of Parkinson's disease (PD), but its central mechanisms remain unclear. Here, we utilize multiple mouse models, which mimic both genetic and sporadic PD, to reproduce PD-related gut motility dysfunction. We find that α-synuclein pathology significantly impairs the excitability of cholinergic neurons in the dorsal motor nucleus of the vagus (DMV). Chemogenetic activation of these neurons effectively restores gut motility in PD models, revealing a causal link between DMV neuronal hypoexcitability and gut motility dysfunction. Notably, electroacupuncture (EA) at ST36, a classic acupoint that activates vagal pathways, robustly increases the excitability of DMV neurons and alleviates gut dysmotility in PD mice, a therapeutic effect mediated by the cholinergic brain-gut axis. Together, our findings demonstrate that DMV neuronal hypoexcitability is a key driver of PD-related gut dysmotility and suggest that EA at ST36 could serve as a promising therapeutic strategy.