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Host oligodendrogli...
Host oligodendrogliopathy and ɑ-synuclein strains dictate disease severity in multiple system atrophy
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- Torre-Muruzabal, Teresa (author)
- KU Leuven, Laboratory for Neurobiology and Gene Therapy, Department of Neurosciences, Leuven, Belgium
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- Van der Perren, Anke (author)
- KU Leuven, Laboratory for Neurobiology and Gene Therapy, Department of Neurosciences, Leuven, Belgium
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- Coens, Audrey (author)
- Institut François Jacob (MIRCen), CEA, and Laboratory of Neurodegenerative Diseases, CNRS, Fontenay-aux-Roses, France
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- Gelders, Géraldine (author)
- KU Leuven, Laboratory for Neurobiology and Gene Therapy, Department of Neurosciences, Leuven, Belgium
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- Janer, Anna Barber (author)
- KU Leuven, Laboratory for Neurobiology and Gene Therapy, Department of Neurosciences, Leuven, Belgium
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- Camacho-Garcia, Sara (author)
- KU Leuven, Laboratory for Neurobiology and Gene Therapy, Department of Neurosciences, Leuven, Belgium
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- Klingstedt, Therése, 1978- (author)
- Linköpings universitet,Kemi,Tekniska fakulteten
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- Nilsson, Peter, 1970- (author)
- Linköpings universitet,Kemi,Tekniska fakulteten
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- Stefanova, Nadia (author)
- Division of Neurobiology, Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria
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- Melki, Ronald (author)
- Institut François Jacob (MIRCen), CEA, and Laboratory of Neurodegenerative Diseases, CNRS, Fontenay-aux-Roses, France
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- Baekelandt, Veerle (author)
- KU Leuven, Laboratory for Neurobiology and Gene Therapy, Department of Neurosciences, Leuven, Belgium
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- Peelaerts, Wouter (author)
- KU Leuven, Laboratory for Neurobiology and Gene Therapy, Department of Neurosciences, Leuven, Belgium
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(creator_code:org_t)
- 2022-02-15
- 2023
- English.
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In: Brain. - : OXFORD UNIV PRESS. - 0006-8950 .- 1460-2156. ; 146:1, s. 237-251
- Related links:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Subject headings
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- Multiple system atrophy is a progressive neurodegenerative disease with prominent autonomic and motor features. During early stages different subtypes of multiple system atrophy are distinguished by their predominant parkinsonian or cerebellar symptoms reflecting the heterogeneous nature of the disease. The pathognomonic feature of multiple system atrophy is the presence of ɑ-synuclein (ɑSyn) protein deposits in oligodendroglial cells. ɑSyn can assemble in specific cellular or disease environments and form ɑSyn strains with unique structural features but the ability of ɑSyn strains to propagate in oligodendrocytes remains elusive. More recently, it was shown that multiple multiple system atrophy strains with related conformations exist in the brain of patients. Here, we investigated if different ɑSyn strains can influence multiple system atrophy progression in a strain-dependent manner. To this aim, we injected two recombinant ɑSyn strains (fibrils and ribbons) in multiple system atrophy transgenic mice and found that ɑSyn protein strains determine disease severity in multiple system atrophy via host-restricted and cell-specific pathology in vivo. ɑSyn strains significantly impact disease progression in a strain-dependent way via oligodendroglial, neurotoxic and immune-related mechanisms. Neurodegeneration and brain atrophy were accompanied by unique microglial and astroglial responses and the recruitment of central and peripheral immune cells. The differential activation of microglial cells correlated with the structural features of ɑSyn strains both in vitro and in vivo. Spectral analysis showed that ribbons propagate oligodendroglial inclusions that are structurally distinct from those of fibrils, with resemblance to oligodendroglial inclusions in multiple system atrophy patient brain. This study therefore shows that the multiple system atrophy phenotype is governed by both the ɑSyn strain nature and the host environment and that by injecting ɑSyn strains in a multiple system atrophy animal model a more comprehensive phenotype can be established.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine (hsv//eng)
Keyword
- multiple system atrophy; neurodegeneration; synucleinopathy; ɑ-synuclein strains
Publication and Content Type
- ref (subject category)
- art (subject category)
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Torre-Muruzabal, ...
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Van der Perren, ...
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Coens, Audrey
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Gelders, Géraldi ...
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Janer, Anna Barb ...
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Camacho-Garcia, ...
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Klingstedt, Ther ...
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Nilsson, Peter, ...
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Stefanova, Nadia
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Melki, Ronald
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Baekelandt, Veer ...
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Peelaerts, Woute ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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Brain
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Linköping University