Stiftung Tierärztliche Hochschule Hannover (TiHo)

Reactive oxygen species are key mediators of demyelination in canine distemper leukoencephalitis but not in Theiler's murine encephalomyelitis

Affiliation
Department of Pathology, University of Veterinary Medicine Hannover, D-30559 Hannover, Germany.
Attig, Friederike;
ORCID
0000-0001-9935-3700
Affiliation
Department of Pathology, University of Veterinary Medicine Hannover, D-30559 Hannover, Germany.
Spitzbarth, Ingo;
Affiliation
Department of Non-clinical Drug Safety, Boehringer Ingelheim Pharma GmbH & Co.KG, D-88397 Biberach, Germany.
Kalkuhl, Arno;
Affiliation
Department of Non-clinical Drug Safety, Boehringer Ingelheim Pharma GmbH & Co.KG, D-88397 Biberach, Germany.
Deschl, Ulrich;
GND
133538087
ORCID
0000-0002-2592-6868
Affiliation
Department of Pathology, University of Veterinary Medicine Hannover, D-30559 Hannover, Germany.
Puff, Christina;
GND
142929565
ORCID
0000-0001-8151-5644
Affiliation
Department of Pathology, University of Veterinary Medicine Hannover, D-30559 Hannover, Germany. wolfgang.baumgaertner@tiho-hannover.de.
Baumgärtner, Wolfgang;
GND
131906879
ORCID
0000-0002-9403-1224
Affiliation
Department of Pathology, University of Veterinary Medicine Hannover, D-30559 Hannover, Germany.
Ulrich, Reiner

(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.

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