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Published in: Acta Neuropathologica 2/2009

01-08-2009 | Original Paper

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

Authors: John P. Rossiter, Lena Hsu, Alan C. Jackson

Published in: Acta Neuropathologica | Issue 2/2009

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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.
Literature
1.
go back to reference Buja LM, Eigenbrodt ML, Eigenbrodt EH (1993) Apoptosis and necrosis: basic types and mechanisms of cell death. Arch Pathol Lab Med 117:1208–1214PubMed Buja LM, Eigenbrodt ML, Eigenbrodt EH (1993) Apoptosis and necrosis: basic types and mechanisms of cell death. Arch Pathol Lab Med 117:1208–1214PubMed
4.
go back to reference Charlton KM, Casey GA (1979) Experimental rabies in skunks: immunofluorescence light and electron microscopic studies. Lab Invest 41:36–44PubMed Charlton KM, Casey GA (1979) Experimental rabies in skunks: immunofluorescence light and electron microscopic studies. Lab Invest 41:36–44PubMed
5.
go back to reference Debnath J, Baehrecke EH, Kroemer G (2005) Does autophagy contribute to cell death? Autophagy 1:66–74PubMed Debnath J, Baehrecke EH, Kroemer G (2005) Does autophagy contribute to cell death? Autophagy 1:66–74PubMed
7.
go back to reference Eskelinen EL (2005) Maturation of autophagic vacuoles in mammalian cells. Autophagy 1:1–10PubMed Eskelinen EL (2005) Maturation of autophagic vacuoles in mammalian cells. Autophagy 1:1–10PubMed
8.
go back to reference Eskelinen EL (2008) To be or not to be? Examples of incorrect identification of autophagic compartments in conventional transmission electron microscopy of mammalian cells. Autophagy 4:257–260PubMed Eskelinen EL (2008) To be or not to be? Examples of incorrect identification of autophagic compartments in conventional transmission electron microscopy of mammalian cells. Autophagy 4:257–260PubMed
11.
go back to reference Hanlon CA, Niezgoda M, Rupprecht CE (2007) Rabies in terrestrial animals. In: Jackson AC, Wunner WH (eds) Rabies, 2 edn edn. Elsevier Academic Press, London, pp 201–258 Hanlon CA, Niezgoda M, Rupprecht CE (2007) Rabies in terrestrial animals. In: Jackson AC, Wunner WH (eds) Rabies, 2 edn edn. Elsevier Academic Press, London, pp 201–258
14.
go back to reference Hicks DJ, Nunez A, Healy DM, Brookes SM, Johnson N, Fooks AR (2009) Comparative pathological study of the murine brain after experimental infection with classical rabies virus and European bat lyssaviruses. J Comp Pathol 140:113–126PubMedCrossRef Hicks DJ, Nunez A, Healy DM, Brookes SM, Johnson N, Fooks AR (2009) Comparative pathological study of the murine brain after experimental infection with classical rabies virus and European bat lyssaviruses. J Comp Pathol 140:113–126PubMedCrossRef
15.
go back to reference Jackson AC (2007) Human disease. In: Jackson AC, Wunner WH (eds) Rabies, 2nd edn. Elsevier Academic Press, London, pp 309–340 Jackson AC (2007) Human disease. In: Jackson AC, Wunner WH (eds) Rabies, 2nd edn. Elsevier Academic Press, London, pp 309–340
17.
go back to reference Johnson N, Mansfield KL, Hicks D et al (2008) Inflammatory responses in the nervous system of mice infected with a street isolate of rabies virus. In: Dodet B, Fooks AR, Müller T, Tordo N et al (eds) Towards the elimination of rabies in Eurasia. Kager, Basel, pp 65–72 Johnson N, Mansfield KL, Hicks D et al (2008) Inflammatory responses in the nervous system of mice infected with a street isolate of rabies virus. In: Dodet B, Fooks AR, Müller T, Tordo N et al (eds) Towards the elimination of rabies in Eurasia. Kager, Basel, pp 65–72
20.
go back to reference Kuzmin IV, Rupprecht CE (2007) Bat rabies. In: Jackson AC, Wunner WH (eds) Rabies, 2nd edn. Elsevier Academic Press, London, pp 259–307 Kuzmin IV, Rupprecht CE (2007) Bat rabies. In: Jackson AC, Wunner WH (eds) Rabies, 2nd edn. Elsevier Academic Press, London, pp 259–307
22.
go back to reference Lycke E, Tsiang H (1987) Rabies virus infection of cultured rat sensory neurons. J Virol 61:2733–2741PubMed Lycke E, Tsiang H (1987) Rabies virus infection of cultured rat sensory neurons. J Virol 61:2733–2741PubMed
23.
go back to reference Mansfield KL, Johnson N, Nunez A, Hicks D, Jackson AC, Fooks AR (2008) Up-regulation of chemokine gene transcripts and T-cell infiltration into the central nervous system and dorsal root ganglia are characteristics of experimental European bat lyssavirus type 2 infection of mice. J Neurovirol 14:218–228. doi:10.1080/13550280802008297 PubMedCrossRef Mansfield KL, Johnson N, Nunez A, Hicks D, Jackson AC, Fooks AR (2008) Up-regulation of chemokine gene transcripts and T-cell infiltration into the central nervous system and dorsal root ganglia are characteristics of experimental European bat lyssavirus type 2 infection of mice. J Neurovirol 14:218–228. doi:10.​1080/​1355028080200829​7 PubMedCrossRef
26.
go back to reference Morimoto K, Hooper DC, Spitsin S, Koprowski H, Dietzschold B (1999) Pathogenicity of different rabies virus variants inversely correlates with apoptosis and rabies virus glycoprotein expression in infected primary neuron cultures. J Virol 73:510–518PubMed Morimoto K, Hooper DC, Spitsin S, Koprowski H, Dietzschold B (1999) Pathogenicity of different rabies virus variants inversely correlates with apoptosis and rabies virus glycoprotein expression in infected primary neuron cultures. J Virol 73:510–518PubMed
27.
go back to reference Murphy FA, Bauer SP, Harrison AK, Winn WC (1973) Comparative pathogenesis of rabies and rabies-like viruses: viral infection and transit from inoculation site to the central nervous system. Lab Invest 28:361–376PubMed Murphy FA, Bauer SP, Harrison AK, Winn WC (1973) Comparative pathogenesis of rabies and rabies-like viruses: viral infection and transit from inoculation site to the central nervous system. Lab Invest 28:361–376PubMed
28.
go back to reference Park CH, Kondo M, Inoue S et al (2006) The histopathogenesis of paralytic rabies in six-week-old C57BL/6 J mice following inoculation of the CVS-11 strain into the right triceps surae muscle. J Vet Med Sci 68:589–595. doi:10.1292/jvms.68.589 PubMedCrossRef Park CH, Kondo M, Inoue S et al (2006) The histopathogenesis of paralytic rabies in six-week-old C57BL/6 J mice following inoculation of the CVS-11 strain into the right triceps surae muscle. J Vet Med Sci 68:589–595. doi:10.​1292/​jvms.​68.​589 PubMedCrossRef
29.
go back to reference Perl DP, Good PF (1991) The pathology of rabies in the central nervous system. In: Baer GM (ed) The natural history of rabies, 2nd edn. CRC Press, Boca Raton, Florida, pp 163–190 Perl DP, Good PF (1991) The pathology of rabies in the central nervous system. In: Baer GM (ed) The natural history of rabies, 2nd edn. CRC Press, Boca Raton, Florida, pp 163–190
30.
go back to reference Rasalingam P, Rossiter JP, Jackson AC (2005) Recombinant rabies virus vaccine strain SAD-L16 inoculated intracerebrally in young mice produces a severe encephalitis with extensive neuronal apoptosis. Can J Vet Res 69:100–105PubMed Rasalingam P, Rossiter JP, Jackson AC (2005) Recombinant rabies virus vaccine strain SAD-L16 inoculated intracerebrally in young mice produces a severe encephalitis with extensive neuronal apoptosis. Can J Vet Res 69:100–105PubMed
31.
go back to reference Rossiter JP, Jackson AC (2007) Pathology. In: Jackson AC, Wunner WH (eds) Rabies, 2nd edn. Elsevier Academic Press, London, pp 383–409 Rossiter JP, Jackson AC (2007) Pathology. In: Jackson AC, Wunner WH (eds) Rabies, 2nd edn. Elsevier Academic Press, London, pp 383–409
32.
go back to reference Scott CA, Rossiter JP, Andrew RD, Jackson AC (2008) Structural abnormalities in neurons are sufficient to explain the clinical disease and fatal outcome in experimental rabies in yellow fluorescent protein-expressing transgenic mice. J Virol 82:513–521. doi:10.1128/JVI.01677-07 PubMedCrossRef Scott CA, Rossiter JP, Andrew RD, Jackson AC (2008) Structural abnormalities in neurons are sufficient to explain the clinical disease and fatal outcome in experimental rabies in yellow fluorescent protein-expressing transgenic mice. J Virol 82:513–521. doi:10.​1128/​JVI.​01677-07 PubMedCrossRef
36.
go back to reference Van Gehuchten A, Nelis C (1900) Les lesions histologiques de la rage chez les animaux et chez l’homme. Bull Acad R Med Belg 14:31–66 Van Gehuchten A, Nelis C (1900) Les lesions histologiques de la rage chez les animaux et chez l’homme. Bull Acad R Med Belg 14:31–66
38.
Metadata
Title
Selective vulnerability of dorsal root ganglia neurons in experimental rabies after peripheral inoculation of CVS-11 in adult mice
Authors
John P. Rossiter
Lena Hsu
Alan C. Jackson
Publication date
01-08-2009
Publisher
Springer-Verlag
Published in
Acta Neuropathologica / Issue 2/2009
Print ISSN: 0001-6322
Electronic ISSN: 1432-0533
DOI
https://doi.org/10.1007/s00401-009-0503-6

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