Objective/Rationale:
The neural network of the gut called the enteric nervous system (ENS) is affected by the pathological process in PD. One of the relevant features of the ENS is its accessibility to biopsies, making it a putative original source of biomarkers for PD. The ENS does not only contain neurons but also enteric glial cells (EGC), the counterpart of the brain astrocytes. The aim of our project is to determine whether these EGC can be a novel source of biomarkers for PD.
Project Description:
The EGC will be analyzed in colonic biopsies of 20 PD patients and 20 control patients. In the first part of the project, we will analyze the expression of different forms of the glial marker GFAP (glial fibrillary acidic protein) in biopsies from PD patients and healthy controls. In a second set of experiments, we will assess the permeability of intestinal epithelial barrier (a layer of polarized epithelial cells that is often considered the digestive counterpart of the central nervous system blood-brain-barrier), which is regulated by the EGC. This will be carried out by analyzing the colonic biopsies using Ussing chambers, a scientific tool to measure ion transport.
Relevance to Diagnosis/Treatment of Parkinson’s Disease:
Development of biomarkers in PD has been hampered by the fact that the core pathology lies in the brain, hidden from direct study in living patients. The recent observations that demonstrated the presence of PD pathology in peripheral neural tissues such as the ENS provide new opportunities to develop original histopathological markers of the disease.
Anticipated Outcome:
The impact of the biomarkers we are seeking to develop is potentially major, because (i) provided the alterations of the EGC are specific to PD, it opens the way to a biochemical and functional diagnosis in the living patient; (ii) according to recent data supporting an early involvement of ENS in PD, it may constitute a preclinical biomarker.
Final Outcome
We have shown that significant changes occur in the enteric glial cells (EGC) in Parkinson’s disease patients, especially regarding one key protein of these cells called GFAP (glial fibrillary acidic protein). The amount of phosphate group was significantly lower in GFAP extracted from gut biopsies of PD patients as compared to healthy subjects or patients with atypical parkinsonism. Our results provide new insights for the development of biomarkers in PD.
June 2014