Oxidative Stress in Transgenic Mice with Oligodendroglial α-Synuclein Overexpression Replicates the Characteristic Neuropathology of Multiple System Atrophy
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Multiple system atrophy (MSA) is a progressive neurodegenerative disorder characterized by parkinsonism unresponsive to dopaminergic therapy, cerebellar ataxia, and dysautonomia. Neuropathology shows a characteristic neuronal multisystem degeneration that is associated with widespread oligodendroglial alpha-synuclein (alpha-SYN) inclusions. Presently no animal model completely replicates the specific neuropathology of MSA. Here we investigated the behavioral and pathological features resulting from oligodendroglial alpha-SYN overexpression in transgenic mice exposed to mitochondrial inhibition by 3-nitropropionic acid. In transgenic mice 3-nitropropionic acid induced or augmented motor deficits that were associated with MSA-like pathology including striatonigral degeneration and olivopontocerebellar atrophy. Widespread astrogliosis and microglial activation were also observed in the presence of alpha-SYN in oligodendrocytes. Our results indicate that combined mitochondrial inhibition and overexpression of oligodendroglial alpha-SYN generates a novel model of MSA that may be useful for evaluating both pathogenesis and treatment strategies.
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Later studies using the same PLP promoter demonstrated subtle motor impairment and a 31.4% loss of nigral neurons.
“Later studies using the same PLP promoter demonstrated subtle motor impairment and a 31.4% loss of nigral neurons [16, 52].”
From Novel oligodendroglial alpha synuclein viral vector models of multiple system atrophy: studies in rodents and nonhuman primates (2017) · cites this paper as [52]
The Locomotor Dysfunction section reports a shorter hindlimb stride length in untreated PLP–α-synuclein mice, and the Striatonigral Neuronal Pathology section reports fewer nigral TH-immunoreactive neurons at baseline. Our copy does not give a 31.4% figure for that loss; the more extensive motor impairment described followed 3-NP treatment. (LLM, conf=0.86)
Experimental — accuracy not yet measuredTransgenic mouse models of MSA overexpressing α-syn in oligodendrocytes presented early and significant microglial activation and related neuroinflammation accompanying α-syn accumulation in oligodendrocytes.
“Transgenetic mouse models of MSA overexpressing α-syn in oligodendrocytes also presented early and significant microglial activation and related neuroinflammation accompanying the α-syn accumulation in oligodendrocytes.292,293”
From Microglia in neurodegenerative diseases: mechanism and potential therapeutic targets (2023) · cites this paper as [293]
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- Authors
- Stefanova, N., Reindl, M., Neumann, M., Haass, C., Poewe, W., Kahle, P. J., & Wenning, G. K.
- Affiliations
- Innsbruck Medical University (AT)
- Ludwig-Maximilians-Universität München (DE)
- Corresponding author
- Wenning, Gregor K.
- ORCID
- Venue
- The American Journal of Pathology
- Publisher
- Elsevier BV
- Published
- 2005-03
- Volume
- 166
- Issue
- 3
- Pages
- 869-876
- ISSN
- 0002-9440 (ISSN-L)
- PMC
- PMC1602361
- OpenAlex
- W2006210634
- Cited by
- 208
- References
- 47
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 8 · 2023: 4 · 2022: 5 · 2021: 7 · 2020: 18 · 2019: 10 · 2018: 10 · 2017: 11 · 2016: 12 · 2015: 13 · 2014: 14 · 2013: 15 · 2012: 7
- FWCI
- 7.12
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- American Journal Of Pathology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Deutsche Forschungsgemeinschaft (SFB 596)
- Topics
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nuclear Receptors and Signaling
- Keywords
- multiple system atrophy, alpha-synuclein, oligodendrocytes, transgenic mice, 3-nitropropionic acid, mitochondrial inhibition, oxidative stress, striatonigral degeneration, olivopontocerebellar atrophy, parkinsonism, astrocyte activation, microglial activation, animal models of neurodegeneration
- MeSH terms
- CD68 Molecule, Animals, Astrocytes, Disease Models, Animal, Image Processing, Computer-Assisted, Immunohistochemistry, Mice, Transgenic, Movement, Movement Disorders, Nerve Tissue Proteins, Neurons, Nitro Compounds, Oligodendroglia, Propionates, Time Factors, Antigens, Differentiation, Myelomonocytic, Antigens, CD, Microglia, Oxidative Stress, Multiple System Atrophy, Mice, Synucleins, alpha-Synuclein
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