Live imaging of neurons and mitochondria in the human enteric nervous system to assess Parkinson’s disease related neurodegeneration

Neurodegenerative disorders, have a large impact on social and economic level; they affect quality of life to a large extent and create high financial burden for patients. Until now the only diagnosis for most of the neurodegenerative diseases is based on clinical symptoms, which occur when the disease is already advanced. Thus, available therapy for neurodegenerative disorders is unfortunately purely symptomatic. Therefore apart from designing new therapies, also identification of useful biomarkers is crucial to improve the early-stage diagnosis. The enteric nervous system (ENS) is a highly organized network of neurons and glial cells localized in two plexus: the myenteric and the submucosal, which regulate various gastrointestinal functions independently from the central nervous system (CNS). It is therefore also referred to as the “brain in the gut”. Compared to the CNS, the ENS has the advantage to be easily accessible via routine intestinal biopsies (obtained during gastroduodenoscopy), which offers an easy and safe way to obtain living human (enteric submucosal) neurons. Parkinson’s disease is also characterized by cellular and molecular abnormalities outside the CNS. Some extra-brain manifestations are hypothesized to predate the motor signals by years, as it is the case for gastrointestinal dysfunction. In fact, α-synuclein aggregates (one of the main pathological features in Parkinson’s disease) have been shown in the ENS of Parkinson’s disease patients and in rodent models for Parkinson’s disease . Moreover, our group has demonstrated that neuronal morphology and function of these neurons can be successfully investigated by microscopic techniques.