Session Information
Date: Monday, June 5, 2017
Session Title: Parkinsonism, MSA, PSP (Secondary and Parkinsonism-Plus)
Session Time: 1:45pm-3:15pm
Location: Exhibit Hall C
Objective: The aim of the present study is to investigate mitochondrial functioning in fibroblasts and iPSC-derived dopaminergic neurons of patients affected by Multiple System Atrophy (MSA) and healthy controls.
Background: The pathogenesis of MSA is still widely unknown. Mitochondrial dysfunction is one of the pathogenetic mechanisms which have been conjectured so far.
Methods: Fibroblasts were isolated from skin biopsies of 7 MSA-P, 7 MSA-C and 5 healthy controls. Fibroblasts underwent several analyses to assess mitochondrial functioning: respiratory chain complexes’ activity (spectrophotometric analyses), respiratory chain complexes amount (WB), O2 consumption (high resolution respirometry), mitochondrial biogenesis (qPCR), mtDNA amount (qPCR).
Induced pluripotent stem cells (iPSCs) were generated from 4 MSA (2 MSA-C and 2 MSA-P) and 4 controls through a viral method. iPSCs were differentiated towards dopaminergic neurons through an already described protocol. Most of the analyses described for fibroblasts (respiratory chain complexes’ amount and activity, mitochondrial biogenesis, mtDNA amount) were performed also on neurons.
Results: MSA fibroblasts showed a mitochondrial deficit in comparison to controls. This observation was supported by the following findings (in some cases statistically significant): a reduction of the activity of respiratory chain (mainly in MSA-C), a reduction of O2 consumption (mainly in MSA-C) and an increase of mtDNA amount.
No statistically significant differences were observed in neurons (probably also because of the limited number of cases and controls), but a trend supported many of the data observed in fibroblasts.
Conclusions: The present study strengthens the hypothesis of a mitochondrial dysfunction in MSA, outlines differences between MSA-P and MSA-C and identifies some possible mechanisms which may be responsible for the mitochondrial defect.
To cite this abstract in AMA style:
G. Monzio Compagnoni, E. Frattini, F. Fortunato, D. Ronchi, A. Bordoni, M. Garbellini, S. Salani, M. Guida, N. Bresolin, S. Corti, G.P. Comi, A. Di Fonzo. Evaluation of mitochondrial dysfunction in fibroblasts and iPSC-derived dopaminergic neurons of patients affected by Multiple System Atrophy [abstract]. Mov Disord. 2017; 32 (suppl 2). https://www.mdsabstracts.org/abstract/evaluation-of-mitochondrial-dysfunction-in-fibroblasts-and-ipsc-derived-dopaminergic-neurons-of-patients-affected-by-multiple-system-atrophy/. Accessed May 17, 2025.« Back to 2017 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/evaluation-of-mitochondrial-dysfunction-in-fibroblasts-and-ipsc-derived-dopaminergic-neurons-of-patients-affected-by-multiple-system-atrophy/