Appraisal of the dopaminergic and noradrenergic innervation of the submucosal plexus in PD.

Abstract

The principal components of the enteric nervous system (ENS) are two neuronal networks, the myenteric and submucosal plexus (SMP), which are primarily involved in the regulation of gastrointestinal (GI) motility and secretion, respectively. These two plexus are made up of intrinsic neurons receiving input from the extrinsic sympathetic and parasympathetic innervation of the gut. Both the intrinsic and extrinsic innervations of the gut are affected by Lewy pathology in Parkinson's disease (PD). A recent autopsy survey indicated that there was no global or dopaminergic loss in the myenteric plexus in PD but the SMP was not examined. The aim of the present work was to compare the relative abundance of dopaminergic and noradrenergic neurons in colonic biopsies between PD patients and control individuals. Colonic biopsies were taken during the course of a colonoscopy in 35 PD patients and 10 control subjects. Density of dopaminergic neurons and expression of the dopaminergic and noradrenergic markers were analyzed by tyrosine hydroxylase (TH) immunofluorescence and Western blot using anti-dopamine transporter (DAT) and anti-dopamine beta-hydroxylase (DBH), respectively. No significant differences were observed in the density of dopaminergic neurons and in the expression levels of dopaminergic and noradrenergic markers in colonic biopsies from PD patients as compared to controls. Our results indicate that there is no evidence of dopaminergic and noradrenergic neuronal loss in the SMP in PD, thereby suggesting that neuropathology in submucosal neurons is unlikely to be a causative factor for GI dysfunction in PD.