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Open AccessArticle

Reactive Oxygen Species Are Key Mediators of Demyelination in Canine Distemper Leukoencephalitis but not in Theiler’s Murine Encephalomyelitis

1
Department of Pathology, University of Veterinary Medicine Hannover, D-30559 Hannover, Germany
2
Center for Systems Neuroscience, D-30559 Hannover, Germany
3
Department of Non-clinical Drug Safety, Boehringer Ingelheim Pharma GmbH & Co.KG, D-88397 Biberach, Germany
4
Institute for Veterinary Pathology, Faculty of Veterinary Medicine, University of Leipzig, D-04103 Leipzig, Germany
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2019, 20(13), 3217; https://doi.org/10.3390/ijms20133217
Received: 15 May 2019 / Revised: 26 June 2019 / Accepted: 28 June 2019 / Published: 30 June 2019
(1) Background: Canine distemper virus (CDV)-induced demyelinating leukoencephalitis (CDV-DL) in dogs and Theiler’s murine encephalomyelitis (TME) virus (TMEV)-induced demyelinating leukomyelitis (TMEV-DL) are virus-induced demyelinating conditions mimicking Multiple Sclerosis (MS). Reactive oxygen species (ROS) can induce the degradation of lipids and nucleic acids to characteristic metabolites such as oxidized lipids, malondialdehyde, and 8-hydroxyguanosine. The hypothesis of this study is that ROS are key effector molecules in the pathogenesis of myelin membrane breakdown in CDV-DL and TMEV-DL. (2) Methods: ROS metabolites and antioxidative enzymes were assessed using immunofluorescence in cerebellar lesions of naturally CDV-infected dogs and spinal cord tissue of TMEV-infected mice. The transcription of selected genes involved in ROS generation and detoxification was analyzed using gene-expression microarrays in CDV-DL and TMEV-DL. (3) Results: Immunofluorescence revealed increased amounts of oxidized lipids, malondialdehyde, and 8-hydroxyguanosine in CDV-DL while TMEV-infected mice did not reveal marked changes. In contrast, microarray-analysis showed an upregulated gene expression associated with ROS generation in both diseases. (4) Conclusion: In summary, the present study demonstrates a similar upregulation of gene-expression of ROS generation in CDV-DL and TMEV-DL. However, immunofluorescence revealed increased accumulation of ROS metabolites exclusively in CDV-DL. These results suggest differences in the pathogenesis of demyelination in these two animal models. View Full-Text
Keywords: canine distemper leukoencephalitis; Theiler’s murine encephalomyelitis; reactive oxygen species; malondialdehyde; E06; 8-hydroxyguanosine; superoxide dismutase; catalase canine distemper leukoencephalitis; Theiler’s murine encephalomyelitis; reactive oxygen species; malondialdehyde; E06; 8-hydroxyguanosine; superoxide dismutase; catalase
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Attig, F.; Spitzbarth, I.; Kalkuhl, A.; Deschl, U.; Puff, C.; Baumgärtner, W.; Ulrich, R. Reactive Oxygen Species Are Key Mediators of Demyelination in Canine Distemper Leukoencephalitis but not in Theiler’s Murine Encephalomyelitis. Int. J. Mol. Sci. 2019, 20, 3217.

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