The presence of Lewy bodies and Lewy neurites (LN) has been demonstrated in the enteric nervous system (ENS) of Parkinson's disease (PD) patients. The aims of the present research were to use routine colonoscopy biopsies (1) to analyze, in depth, enteric pathology throughout the colonic submucosal plexus (SMP), and (2) to correlate the pathological burden with neurological and gastrointestinal (GI) symptoms. A total of 10 control and 29 PD patients divided into 3 groups according to disease duration were included. PD and GI symptoms were assessed using the Unified Parkinson's Disease Rating Scale part III and the Rome III questionnaire, respectively. Four biopsies were taken from the ascending and descending colon during the course of a total colonoscopy. Immunohistochemical analysis was performed using antibodies against phosphorylated alpha-synuclein, neurofilaments NF 220 kDa (NF) and tyrosine hydroxylase (TH). The density of LN, labeled by anti-phosphorylated alpha-synuclein antibodies, was evaluated using a quantitative rating score. Lewy pathology was apparent in the colonic biopsies from 21 patients and in none of the controls. A decreased number of NF-immunoreactive neurons per ganglion was observed in the SMP of PD patients compared to controls. The amount of LN in the ENS was inversely correlated with neuronal count and positively correlated with levodopa-unresponsive features and constipation. Analysis of the ENS by routine colonoscopy biopsies is a useful tool for pre-mortem neuropathological diagnosis of PD, and also provides insight into the progression of motor and non-motor symptoms.

Functional and morphological alterations of the intestinal epithelial barrier (IEB) have been consistently reported in digestive disorders such as irritable bowel syndrome and inflammatory bowel disease. There is mounting evidence that Parkinson’s disease (PD) is not only a brain disease but also a digestive disorder. Gastrointestinal involvement is a frequent and early event in the course of PD, and it may be critically involved in the early development of the disease. We therefore undertook the present survey to investigate whether changes in the IEB function and/or morphology occur in PD. Colonic biopsies were performed in 31 PD patients and 11 age-matched healthy controls. The para- and transcellular permeability were evaluated by measuring sulfonic acid and horseradish peroxidase flux respectively, in colonic biopsies mounted in Ussing chambers. The expression and localization of the two tight junctions proteins ZO-1 and occludin were analyzed by Western blot and immunofluorescence, respectively. The para- and transcellular permeability were not different between PD patients and controls. The expression of occludin, but not ZO-1, was significantly lower in colonic samples from PD patients as compared to controls and the cellular distribution of both proteins was altered in colonic mucosal specimens from PD patients. Our findings provide evidence that the IEB is morphologically altered in PD and further reinforce the potential role of the gastrointestinal tract in the initiation and/or the progression of the disease.

Lewy pathology in Parkinson disease (PD) extends well beyond the CNS, also affecting peripheral autonomic neuronal circuits, especially the enteric nervous system (ENS). The ENS is an integrative neuronal network also referred to as “the brain in the gut” because of its similarities to the CNS. We have recently shown that the ENS can be readily analyzed using routine colonic biopsies. This led us to propose that the ENS could represent a unique window to assess the neuropathology in living patients with PD. In this perspective, we discuss current evidence which indicates that the presence of ENS pathology may by exploited to improve our understanding and management of PD and likely other neurodegenerative disorders.