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Neurotoxocarosis alters myelin protein gene transcription and expression

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Abstract

Neurotoxocarosis is an infection of the central nervous system caused by migrating larvae of the common dog and cat roundworms (Toxocara canis and Toxocara cati), which are zoonotic agents. As these parasites are prevalent worldwide and neuropathological and molecular investigations on neurotoxocarosis are scare, this study aims to characterise nerve fibre demyelination associated with neurotoxocarosis on a molecular level. Transcription of eight myelin-associated genes (Cnp, Mag, Mbp, Mog, Mrf-1, Nogo-A, Plp1, Olig2) was determined in the mouse model during six time points of the chronic phase of infection using qRT-PCR. Expression of selected proteins was analysed by Western blotting or immunohistochemistry. Additionally, demyelination and neuronal damage were investigated histologically. Significant differences (p ≤ 0.05) between transcription rates of T. canis-infected and uninfected control mice were detected for all analysed genes while T. cati affected five of eight investigated genes. Interestingly, 2′, 3 ´-cyclic nucleotide 3′-phosphodiesterase (Cnp) and myelin oligodendrocyte glycoprotein (Mog) were upregulated in both T. canis- and T. cati-infected mice preceding demyelination. Later, CNPase expression was additionally enhanced. As expected, myelin basic protein (Mbp) was downregulated in cerebra and cerebella of T. canis-infected mice when severe demyelination was present 120 days post infectionem (dpi). The transcriptional pattern observed in the present study appears to reflect direct traumatic and hypoxic effects of larval migration as well as secondary processes including host immune reactions, demyelination and attempts to remyelinate damaged areas.

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Acknowledgments

The authors thank Annika Lehmbecker, PhD, for valuable support in histological photography and Bettina Buck, Petra Grünig and Sabine Händel for excellent technical assistance. Furthermore, the PhD grants of the Society of Friends of the University of Veterinary Medicine Hannover [“Gesellschaft der Freunde der Tierärztlichen Hochschule Hannover” (GdF)] and the Hannover Graduate School for Veterinary Pathobiology, Neuroinfectiology and Translational Medicine (HGNI) for LH are gratefully acknowledged.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Institute for Parasitology, University of Veterinary Medicine Hannover, Buenteweg 17, 30559, Hannover, Germany

    Lea Heuer & Christina Strube

  2. Institute for Biometry, Epidemiology and Information Processing, University of Veterinary Medicine Hannover, Buenteweg 2, 30559, Hannover, Germany

    Martin Beyerbach

  3. Department of Neuroimmunology, Institute for Multiple Sclerosis Research, The Hertie Foundation, Waldweg 33, 37073, Göttingen, Germany

    Fred Lühder

  4. Max Planck Institute for Experimental Medicine, University of Göttingen Medical School, Hermann-Rein-Str. 3, 37075, Göttingen, Germany

    Fred Lühder

  5. Department of Pathology, University of Veterinary Medicine Hannover, Buenteweg 17, 30559, Hannover, Germany

    Andreas Beineke

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  1. Lea Heuer
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  3. Fred Lühder
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  4. Andreas Beineke
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Correspondence to Christina Strube.

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Heuer, L., Beyerbach, M., Lühder, F. et al. Neurotoxocarosis alters myelin protein gene transcription and expression. Parasitol Res 114, 2175–2186 (2015). https://doi.org/10.1007/s00436-015-4407-1

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  • DOI: https://doi.org/10.1007/s00436-015-4407-1

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