Vagal motoneurons in Parkinson’s disease

The dorsal motor nucleus of the vagus nerve (DMV) is among the first regions affected by Lewy pathology in Parkinson’s disease (PD). Neuropathology in the DMV is thought to contribute to the prodromal non-motor manifestations of disease, such as a decline in gastrointestinal motility. Because vagal motoneurons are affected so early in PD, considerable efforts have focused on understanding their role in the pathogenic and progressive mechanisms of the disease. Two distinct theories that explain the origin of DMV pathology have been proposed. The first states that cell-autonomous characteristics determine neuronal susceptibility to environmental, genetic, or age-related disease contributors. The second prion-like hypothesis attributes the pathogenesis and progression of disease to processes of protein misfolding, seeding, and perpetual self-replication. These aberrant protein species are thought to propagate pathology by cell-to-cell transfer through neuronal networks. We will discuss experimental evidence for the involvement of the DMV in each of these hypotheses. We propose that a consideration of cell-autonomous factors could be useful to explain how prion-like protein pathology progresses through complex neuronal networks to affect only certain predisposed neuronal populations.