Affiliation:
1. Section of Cellular and Molecular Neurobiology IRCCS Mondino Foundation Pavia Italy
2. Department of Brain and Behavioral Sciences University of Pavia Pavia Italy
3. Unit of Movement Disorders IRCCS Mondino Foundation Pavia Italy
4. Section of Sleep Medicine and Epilepsy IRCCS Mondino Foundation Pavia Italy
5. Neurorehabilitation Unit IRCCS Mondino Foundation Pavia Italy
6. Department of Molecular Medicine University of Pavia Pavia Italy
7. Neurogenetics Unit IRCCS Mondino Foundation Pavia Italy
8. IRCCS Ca’ Granda Ospedale Maggiore Policlinico Milan Italy
Abstract
AbstractBackgroundIdiopathic rapid eye movement (REM) sleep behavior disorder (iRBD) is associated with prodromal Parkinson's disease (PD), but the mechanisms linking phenoconversion of iRBD to PD have not yet been clarified. Considering the association between mitochondrial dysfunction and sleep disturbances in PD, we explored mitochondrial activity in fibroblasts derived from iRBD patients to identify a biochemical profile that could mark the presence of impending neurodegeneration.MethodsThe study involved 28 participants, divided into three groups: patients diagnosed with iRBD, PD patients converted from iRBD (RBD‐PD), and healthy controls. We performed a comprehensive assessment of mitochondrial function, including an examination of mitochondrial morphology, analysis of mitochondrial protein expression levels by western blot, and measurement of mitochondrial respiration using the Seahorse XFe24 analyzer.ResultsIn basal conditions, mitochondrial respiration did not differ between iRBD and control fibroblasts, but when cells were challenged with a higher energy demand, iRBD fibroblasts exhibited a significant (P = 0.006) drop in maximal and spare respiration compared to controls. Interestingly, RBD‐PD patients showed the same alterations with a further significant reduction in oxygen consumption linked to adenosine triphosphate production (P = 0.032). Moreover, RBD‐PD patients exhibited a significant decrease in protein levels of complexes III (P = 0.02) and V (P = 0.002) compared to controls, along with fragmentation of the mitochondrial network. iRBD patients showed similar, but milder alterations.ConclusionsAltogether, these findings suggest that mitochondrial dysfunctions in individuals with iRBD might predispose to worsening of the bioenergetic profile observed in RBD‐PD patients, highlighting these alterations as potential predictors of phenoconversion to PD. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Subject
Neurology (clinical),Neurology