ENTERIC NERVOUS SYSTEM IN PARKINSON’S DISEASE: INCREASED MITOCHONDRIAL DENSITY BUT REDUCED GANGLIA VOLUME

Objectives Presumably, idiopathic Parkinson’s disease (IPD) starts at the enteric level and it is widely accepted that mitochondria play a crucial role in the pathopysiological cascade of this disease. In this study we analyze colonic submucosal morphometric sof ganglia and inclosed mitochondria. Methodology Proximal and distal colon biopsies were collected from 11 IPD patients and 4 healthy controls. 65 ganglia from patients and 41 from controls were analyzed via a combination of immunofluorescence, confocal microscopy, and advanced image analysis targeting mitochondrial morphometrics and ganglia volumes. Results Mitochondrial density in ganglia (p = 0.043) and normalized mitochondrial mass (p = 0.017) were significantly increased in patients. In left patient colon, mean mitochondrial volume was larger than in the right colon (p = 0.028). Furthermore, patient data showed an inverse correlation between mean mitochondrial volume and the UPDRS motor score (p= 0.04). In controls, in contrast, such a gradient was not observed. Ganglia volumes, serving as a surrogate for submucosal neurodegeneration, were significantly reduced in patients (p=0.005). Conclusion Here we provide the first ex vivo proof of mitochondrial dysfunction in the enteric nervous system of IPD patients and thereby confirm mitochondrial involvement at this level of pathophysiology.