Objective: Study in vivo mitochondrial and ganglionic morphometrics of enteric neurons in Parkinson’s disease.

Background: While well established in autopsy studies, the crucial role of mitochondria in the pathophysiological cascade of Parkinson’s disease still lacks proof. In this context in vivo brain studies are not feasible, but surrogate studies in the gut are promising as the disease presumably starts at the enteric level.

Methods: After collecting distal and proximal colon biopsies from 11 Parkinson’s disease patients without clinically apparent gastrointestinal dysfunction and from 4 healthy, age-matched controls, we examined 65 ganglia from patients and 41 from controls. Results were analyzed by single-feature statistics and support vector machines combining the cumulated information from multiple mitochondrial features for classifying patient and control samples.

Results: In patients, mitochondrial count in ganglia (p = 0.043) and normalized mitochondrial mass (p = 0.017) are higher than in controls. In patients but not in controls, the mean mitochondrial volume is smaller in right than left colon (p = 0.003); it also decreases with deteriorating UPDRS motor score (p = 0.04). Ganglia volume, a surrogate for neurodegeneration, is smaller in right colon ganglia of patients than in right colon of controls (p < 0.001). This marker has predictive power for distinguishing patients from controls as shown by receiver operator characteristic. The separate analysis of single mitochondrial features shows significant mitochondrial changes in five out of seven mitochondrial features in left patient colon as compared to controls. Support vector machine analysis and receiver operator characteristic also show mitochondrial changes in the right colon.

Conclusions: This is the first in vivo proof of morphometric changes of mitochondria in the enteric nervous system of Parkinson’s disease patients. In left colon, mitochondrial fragmentation and increase in mitochondrial mass but unchanged ganglia volumes indicate mitochondrial stress and neuroprotective mitochondrial compensation. The data further suggests that such neuroprotective compensation may already have failed in the right colon.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/enteric-neurons-reveal-substantial-in-vivo-mitochondrial-changes-in-parkinsons-disease/