Objective/Rationale:
Central and peripheral inflammations are likely to be critical in the initiation and/or development of PD. Data from recent genetic studies suggest a link between PD and gut inflammation. Whether gastrointestinal inflammation occurs in PD patients has not been addressed yet. Thus, our study aims at determining whether the major pro-inflammatory cytokines are up regulated in the gastrointestinal tract in PD and whether their expression levels correlate with neurologic or digestive symptoms.
Project Description:
Colonic biopsies used for the present study (2 in the ascending colon, 2 in the descending colon) have already been performed in 19 PD patients, 14 control subjects and 6 patients with progressive supranuclear palsy and multiple system atrophy. Each PD patient had a neurological (disease duration, UPDRS III score, cumulative dose of levodopa) and gastrointestinal assessment (Rome III score). The mRNA expression levels of pro-inflammatory cytokines (tumor necrosis factor alpha, interferon gamma and interleukin-6, interleukin-1 beta and interleukin-17) and glial marker (Glial fibrillary acidic protein, Sox-10 and S100-beta) will be analyzed by qPCR in two-pooled biopsies. When positive, the results obtained by qPCR will be confirmed at the protein level either by Elisa and/or Western Blot.
Relevance to Diagnosis/Treatment of Parkinson’s Disease:
In view of recent findings, the gut appears as a primary target organ in PD. The gastrointestinal tract is the main area of exchange between exogenous factors and host neuronal and immune cells. Preliminary profiling of inflammation in the gut as proposed in our survey is a prerequisite for pursuing research in the field of inflammation in PD. This will set the basis for further investigations addressing the causative role of intestinal inflammation in PD.
Anticipated Outcome:
We anticipate that the present study will demonstrate that the main pro-inflammatory cytokines and glial markers are up regulated in the gastrointestinal tract, thereby suggesting that inflammation is present within the gut of PD patients.