Session Information
Date: Monday, June 20, 2016
Session Title: Parkinsonism, MSA, PSP (secondary and parkinsonism-plus)
Session Time: 12:30pm-2:00pm
Location: Exhibit Hall located in Hall B, Level 2
Objective: The aim of the present study is to generate dopaminergic and pyramidal neurons from iPSCs of MSA patients in order to establish an in vitro model that will contribute to unravel the pathogenesis of the disease.
Background: Multiple System Atrophy is a neurodegenerative disease characterized by the involvement of several neuronal systems including midbrain dopamineregic neurons and upper motor neurons.
Methods: iPSCs were generated from skin-biopsy-derived fibroblasts of 2 MSA-C and 3 MSA-P patients. Alpha-synuclein expression was evaluated in patient-derived iPSCs and in three control iPSC-lines through RT-PCR, Western Blot and Immunocytochemistry. iPSCs were differentiated towards dopaminergic and glutamatergic neurons and were characterized through ICC (Beta-III-Tubulin, MAP2, TH, GIRK2, VGLUT1, Alpha-synuclein, Phosphorylated-alpha-synuclein).
Results: iPSCs were generated and pluripotency was confirmed assessing the expression of the markers OCT, SSEA-4, TRA1-60, SOX2. Alpha-synuclein was diffusely expressed in iPSCs, with high variability among samples and no statistically significant expression differences between patients and controls. Differentiation towards pyramidal and dopaminergic neurons was proved by morphology and expression of specific markers. Alpha-synuclein was expressed in neurons with a diffuse cytoplasmic localization. Nor intracellular alpha-synuclein aggregates were detected neither different staining between patients and control was found. Differently, phosphorylated-alpha-synuclein appeared to be more expressed in patients’ iPSC-derived neurons than in controls.
Conclusions: The present study provides a iPSC-based model of MSA and suggests a pathogenic role of phosphorylated alpha-synuclein in the iPSC-derived neurons of MSA patients.
To cite this abstract in AMA style:
G. Monzio Compagnoni, E. Frattini, S. Salani, F. Fortunato, N. Bresolin, S. Corti, G.P. Comi, A. Di Fonzo. Generation and characterization of iPSC-derived nigral dopaminergic and pyramidal glutamatergic neurons from patients affected by multiple system atrophy [abstract]. Mov Disord. 2016; 31 (suppl 2). https://www.mdsabstracts.org/abstract/generation-and-characterization-of-ipsc-derived-nigral-dopaminergic-and-pyramidal-glutamatergic-neurons-from-patients-affected-by-multiple-system-atrophy/. Accessed May 9, 2025.« Back to 2016 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/generation-and-characterization-of-ipsc-derived-nigral-dopaminergic-and-pyramidal-glutamatergic-neurons-from-patients-affected-by-multiple-system-atrophy/