Progressive striatonigral degeneration in a transgenic mouse model of multiple system atrophy: translational implications for interventional therapies

Acta Neuropathologica Communications
Violetta RefoloNadia Stefanova

Abstract

Multiple system atrophy (MSA) is a rapidly progressive neurodegenerative disorder characterized by widespread oligodendroglial cytoplasmic inclusions of filamentous α-synuclein, and neuronal loss in autonomic centres, basal ganglia and cerebellar circuits. It has been suggested that primary oligodendroglial α-synucleinopathy may represent a trigger in the pathogenesis of MSA, but the mechanisms underlying selective vulnerability and disease progression are unclear. The post-mortem analysis of MSA brains provides a static final picture of the disease neuropathology, but gives no clear indication on the sequence of pathogenic events in MSA. Therefore, alternative methods are needed to address these issues. We investigated selective vulnerability and disease progression in the transgenic PLP-α-syn mouse model of MSA characterized by targeted oligodendroglial α-synuclein overexpression aiming to provide a neuropathological correlate of motor deterioration. We show progressive motor deficits that emerge at 6 months of age and deteriorate up to 18 months of follow-up. The motor phenotype was associated with dopaminergic cell loss in the substantia nigra pars compacta at 6 months, followed by loss of striatal dopaminergic terminals an...Continue Reading

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Citations

Nov 20, 2018·Movement Disorders : Official Journal of the Movement Disorder Society·Antonio Heras-GarvinNadia Stefanova
Jun 11, 2019·PloS One·Christine KaindlstorferGregor Karl Wenning
Jun 13, 2019·Clinical Autonomic Research : Official Journal of the Clinical Autonomic Research Society·Alain NdayisabaNadia Stefanova
Jan 26, 2020·Journal of Neuroinflammation·Antonio Heras-GarvinNadia Stefanova
Jan 11, 2020·Clinical Autonomic Research : Official Journal of the Clinical Autonomic Research Society·Alain Ndayisaba, Gregor K Wenning
Feb 18, 2020·Journal of Neural Transmission·Micaela Johanna GlatDaniel Offen
Nov 20, 2019·Experimental & Molecular Medicine·He-Jin LeeSeung-Jae Lee
May 20, 2020·Brain : a Journal of Neurology·Zhenwei YuJing Zhang
Jun 6, 2020·Investigative Ophthalmology & Visual Science·Kathrin KaehlerAlexandra Koschak
Jul 3, 2019·Frontiers in Cellular Neuroscience·Violetta Refolo, Nadia Stefanova
Mar 19, 2019·Frontiers in Neuroscience·Alain NdayisabaGregor K Wenning
Feb 26, 2020·Translational Neurodegeneration·Seiji KajiRyosuke Takahashi
Apr 16, 2020·Movement Disorders : Official Journal of the Movement Disorder Society·Miguel Lopez-CuinaPierre-Olivier Fernagut
Oct 28, 2020·Movement Disorders : Official Journal of the Movement Disorder Society·Alexey A ShadrinManu Sharma
Dec 5, 2020·Neuropathology and Applied Neurobiology·Marc DeffainsPierre-Olivier Fernagut
Nov 23, 2020·Neurobiology of Disease·David J MarmionJeffrey H Kordower
Jul 9, 2021·Movement Disorders : Official Journal of the Movement Disorder Society·Antonio Heras-GarvinNadia Stefanova
Oct 7, 2021·Journal of Neural Transmission·David J MarmionJeffrey H Kordower

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Methods Mentioned

BETA
transgenic
Protein Assay
ELISA
light microscopy
confocal microscopy
dissection

Software Mentioned

ImageJ
MicroBrightField
StereoInvestigator
Huygens Professional
Leica LAS X

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