iPSC-Derived Striatal Medium Spiny Neurons from Patients with Multiple System Atrophy Show Hypoexcitability and Elevated α-Synuclein Release
Summary
Multiple system atrophy of the parkinsonian type (MSA-P) is a rare, fatal neurodegenerative disease with sporadic onset. It is still unknown if MSA-P is a primary oligodendropathy or caused by neuronal pathophysiology leading to severe, α-synuclein-associated neurodegeneration, mainly in the striatum. In this study, we generated and differentiated induced pluripotent stem cells (iPSCs) from patients with the clinical diagnosis of probable MSA-P (n = 3) and from three matched healthy controls into GABAergic striatal medium spiny neurons (MSNs). We found a significantly elevated release and neuronal distribution for α-synuclein, as well as hypoexcitability in the MSNs derived from the MSA-P patients compared to the healthy controls. These data suggest that the striatal hypoexcitable neurons of MSA-P patients contribute to a pathological α-synuclein burden which is likely to spread to neighboring cells and projection targets, facilitating disease progression.
| Authors | Henkel LM, Kankowski S, Moellenkamp TM, Smandzich NJ, Schwarz S, Di Fonzo A, Göhring G, Höglinger G, Wegner F |
|---|---|
| Journal | Cells |
| Publication Date | 2023 Jan 4;12(2) |
| PubMed | 36672158 |
| PubMed Central | PMC9856678 |
| DOI | 10.3390/cells12020223 |