Altered Expression of D1 and D2 Dopamine Receptors in Vagal Neurons Innervating the Gastric Muscularis Externa in a Parkinson's Disease Rat Model.

Abstract

Parkinson's disease (PD) is characterized by dopaminergic neuron degeneration in the substantia nigra (SN) accompanied by pathology of the dorsal motor nucleus of the vagus (DMV). Gastroparesis is a common non-motor system symptom of PD in patients and in animal models. However, the underlying mechanism of this symptom is not clear. We previously reported on the expression of enhanced tyrosine hydroxylase (TH) and decreased choline acetyltransferase (ChAT) in the DMV of a PD animal model and colocalization of TH and ChAT with the dopamine receptors D1 and D2. We hypothesize that these receptors might contribute to the delayed gastric emptying observed in PD. To investigate the distribution of D1 and D2 in gastric-projecting DMV neurons and alteration of their distribution in a PD rat model. Retrograde tracing, double-labeling immunofluorescence techniques and western blotting were used. After injection of the retrograde tracer fluoro-gold (FG) into the gastric wall, FG-labeled gastric-projecting motoneurons were observed in the caudal and rostral parts of the DMV, and neurons with D1-, D2- and ChAT- immunoreactivity (IR) were widely colocalized in the DMV. Many TH-IR fibers were observed around the D1- and D2-IR neurons. Moreover, decreased D1 and enhanced D2 expression in the DMV was observed in 6-hydroxydopamine (6-OHDA) rats that were treated with a bilateral microinjection of 6-OHDA in the SN. The results indicate that dopamine receptors might affect the activity of gastric-projecting neurons in the DMV, their altered expression may contribute to the gastroparesis observed in PD.