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

Abstract

(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.

• Authors: Friederike Attig, Ingo Spitzbarth, Arno Kalkuhl, Ulrich Deschl, Christina Puff, Wolfgang Baumgärtner, Reiner Ulrich
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 20 Issue 13 (Jun 30 2019) ISSN: 1422-0067 [Electronic] Switzerland
• PMID: 31262031 (Publication Type: Journal Article)

Chemical References

• Reactive Oxygen Species
• Catalase
• Superoxide Dismutase

Topics

• Animals
• Catalase (metabolism)
• Distemper (metabolism, pathology)
• Dogs
• Encephalitis, Viral (metabolism, pathology, virology)
• Female
• Male
• Mice
• Myelin Sheath (metabolism, pathology)
• Reactive Oxygen Species (metabolism)
• Spinal Cord (metabolism, pathology)
• Superoxide Dismutase (metabolism)
• Theilovirus (pathogenicity)