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Selective vulnerability of dorsal root ganglia neurons in experimental rabies after peripheral inoculation of CVS-11 in adult mice

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Abstract

The involvement of dorsal root ganglia was studied in an in vivo model of experimental rabies virus infection using the challenge virus standard (CVS-11) strain. Dorsal root ganglia neurons infected with CVS in vitro show prolonged survival and few morphological changes, and are commonly used to study the infection. It has been established that after peripheral inoculation of mice with CVS the brain and spinal cord show relatively few neurodegenerative changes, but detailed studies of pathological changes in dorsal root ganglia have not previously been performed in this in vivo experimental model. In this study, adult ICR mice were inoculated in the right hindlimb footpad with CVS. Spinal cords and dorsal root ganglia were evaluated at serial time points for histopathological and ultrastructural changes and for biochemical markers of cell death. Light microscopy showed multifocal mononuclear inflammatory cell infiltrates in the sensory ganglia and a spectrum of degenerative neuronal changes. Ultrastructural changes in gangliocytes included features characteristic of the axotomy response, the appearance of numerous autophagic compartments, and aggregation of intermediate filaments, while the neurons retained relatively intact mitochondria and plasma membranes. Later in the process, there were more extensive degenerative neuronal changes without typical features of either apoptosis or necrosis. The degree of degenerative neuronal changes in gangliocytes contrasts with observations in CNS neurons in experimental rabies. Hence, gangliocytes exhibit selective vulnerability in this animal model. This contrasts markedly with the fact that they are, unlike CNS neurons, highly permissive to CVS infection in vitro. Further study is needed to determine mechanisms for this selective vulnerability, which will give us a better understanding of the pathogenesis of rabies.

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Acknowledgments

The authors are grateful for monoclonal antibody 5DF12 from Alexander I. Wandeler (Centre for Rabies Expertise, Canadian Food Inspection Agency, Nepean, Ontario). This work was supported by Canadian Institutes of Health Research Grant MOP-64376, and the Queen’s University Violet E. Powell Research Fund (all to A.C. Jackson). The authors wish to express their gratitude to Frederick A. Murphy (University of Texas Medical Branch, Galveston, TX, USA) for reviewing the electron micrographs.

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Authors and Affiliations

  1. Department of Pathology and Molecular Medicine, Queen’s University, Kingston, ON, Canada

    John P. Rossiter

  2. Department of Microbiology and Immunology, Queen’s University, Kingston, ON, Canada

    Lena Hsu

  3. Departments of Internal Medicine (Neurology) and of Medical Microbiology, University of Manitoba, Winnipeg, MB, Canada

    Alan C. Jackson

  4. Health Sciences Centre, GF-543, 820 Sherbrook Street, Winnipeg, MB, R3A 1R9, Canada

    Alan C. Jackson

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  1. John P. Rossiter
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Correspondence to Alan C. Jackson.

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Rossiter, J.P., Hsu, L. & Jackson, A.C. Selective vulnerability of dorsal root ganglia neurons in experimental rabies after peripheral inoculation of CVS-11 in adult mice. Acta Neuropathol 118, 249–259 (2009). https://doi.org/10.1007/s00401-009-0503-6

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