1887

Abstract

Rabies is an acute viral infection of the central nervous system and is typically fatal in humans and animals; however, its pathogenesis remains poorly understood. In this study, the morphological changes of dendrites and dendritic spines in the CA1 region of the hippocampus were investigated in mice that were infected intracerebrally with an MRV strain of the street rabies virus. Haematoxylin and eosin and fluorescence staining analysis of brain sections from the infected mice showed very few morphological changes in the neuronal bodies and neuronal processes. However, we found a significant decrease in the number of dendritic spines. Primary neuronal cultures derived from the hippocampus of mice (embryonic day 16.5) that were infected with the virus also showed an obvious decrease in the number of dendritic spines. Furthermore, the decrease in the number of dendritic spines was related to the depolymerization of actin filaments (F-actin). We propose that the observed structural changes can partially explain the severe clinical disease that was found in experimental models of street rabies virus infections.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.047480-0
2013-02-01
2019-10-18
Loading full text...

Full text loading...

/deliver/fulltext/jgv/94/2/276.html?itemId=/content/journal/jgv/10.1099/vir.0.047480-0&mimeType=html&fmt=ahah

References

  1. Ackermann M. , Matus A. . ( 2003; ). Activity-induced targeting of profilin and stabilization of dendritic spine morphology. . Nat Neurosci 6:, 1194–1200. [CrossRef] [PubMed]
    [Google Scholar]
  2. Allison D. W. , Gelfand V. I. , Spector I. , Craig A. M. . ( 1998; ). Role of actin in anchoring postsynaptic receptors in cultured hippocampal neurons: differential attachment of NMDA versus AMPA receptors. . J Neurosci 18:, 2423–2436.[PubMed]
    [Google Scholar]
  3. Bamburg J. R. . ( 1999; ). Proteins of the ADF/cofilin family: essential regulators of actin dynamics. . Annu Rev Cell Dev Biol 15:, 185–230. [CrossRef] [PubMed]
    [Google Scholar]
  4. Bloom O. , Evergren E. , Tomilin N. , Kjaerulff O. , Löw P. , Brodin L. , Pieribone V. A. , Greengard P. , Shupliakov O. . ( 2003; ). Colocalization of synapsin and actin during synaptic vesicle recycling. . J Cell Biol 161:, 737–747. [CrossRef] [PubMed]
    [Google Scholar]
  5. Bouzamondo E. , Ladogana A. , Tsiang H. . ( 1993; ). Alteration of potassium-evoked 5-HT release from virus-infected rat cortical synaptosomes. . Neuroreport 4:, 555–558. [CrossRef] [PubMed]
    [Google Scholar]
  6. Capani F. , Martone M. E. , Deerinck T. J. , Ellisman M. H. . ( 2001; ). Selective localization of high concentrations of F-actin in subpopulations of dendritic spines in rat central nervous system: a three-dimensional electron microscopic study. . J Comp Neurol 435:, 156–170. [CrossRef] [PubMed]
    [Google Scholar]
  7. Ceccaldi P. E. , Valtorta F. , Braud S. , Hellio R. , Tsiang H. . ( 1997; ). Alteration of the actin-based cytoskeleton by rabies virus. . J Gen Virol 78:, 2831–2835.[PubMed]
    [Google Scholar]
  8. Dhingra V. , Li X. , Liu Y. , Fu Z. F. . ( 2007; ). Proteomic profiling reveals that rabies virus infection results in differential expression of host proteins involved in ion homeostasis and synaptic physiology in the central nervous system. . J Neurovirol 13:, 107–117. [CrossRef] [PubMed]
    [Google Scholar]
  9. Fath T. , Ke Y. D. , Gunning P. , Götz J. , Ittner L. M. . ( 2009; ). Primary support cultures of hippocampal and substantia nigra neurons. . Nat Protoc 4:, 78–85. [CrossRef] [PubMed]
    [Google Scholar]
  10. Fiala J. C. , Spacek J. , Harris K. M. . ( 2002; ). Dendritic spine pathology: cause or consequence of neurological disorders?. Brain Res Brain Res Rev 39:, 29–54. [CrossRef] [PubMed]
    [Google Scholar]
  11. Fischer M. , Kaech S. , Wagner U. , Brinkhaus H. , Matus A. . ( 2000; ). Glutamate receptors regulate actin-based plasticity in dendritic spines. . Nat Neurosci 3:, 887–894. [CrossRef] [PubMed]
    [Google Scholar]
  12. Glantz L. A. , Lewis D. A. . ( 2000; ). Decreased dendritic spine density on prefrontal cortical pyramidal neurons in schizophrenia. . Arch Gen Psychiatry 57:, 65–73.[CrossRef]
    [Google Scholar]
  13. Gu Y. Y. , Zhang H. Y. , Zhang H. J. , Li S. Y. , Ni J. H. , Jia H. T. . ( 2006; ). 8-Chloro-adenosine inhibits growth at least partly by interfering with actin polymerization in cultured human lung cancer cells. . Biochem Pharmacol 72:, 541–550. [CrossRef] [PubMed]
    [Google Scholar]
  14. Harris K. M. . ( 1999; ). Structure, development, and plasticity of dendritic spines. . Curr Opin Neurobiol 9:, 343–348. [CrossRef] [PubMed]
    [Google Scholar]
  15. Hemachudha T. , Laothamatas J. , Rupprecht C. E. . ( 2002; ). Human rabies: a disease of complex neuropathogenetic mechanisms and diagnostic challenges. . Lancet Neurol 1:, 101–109. [CrossRef] [PubMed]
    [Google Scholar]
  16. Hering H. , Sheng M. . ( 2001; ). Dendritic spines: structure, dynamics and regulation. . Nat Rev Neurosci 2:, 880–888. [CrossRef] [PubMed]
    [Google Scholar]
  17. Hotulainen P. , Paunola E. , Vartiainen M. K. , Lappalainen P. . ( 2005; ). Actin-depolymerizing factor and cofilin-1 play overlapping roles in promoting rapid F-actin depolymerization in mammalian nonmuscle cells. . Mol Biol Cell 16:, 649–664. [CrossRef] [PubMed]
    [Google Scholar]
  18. Hutsler J. J. , Zhang H. . ( 2010; ). Increased dendritic spine densities on cortical projection neurons in autism spectrum disorders. . Brain Res 1309:, 83–94. [CrossRef] [PubMed]
    [Google Scholar]
  19. Ivanov A. , Esclapez M. , Pellegrino C. , Shirao T. , Ferhat L. . ( 2009; ). Drebrin A regulates dendritic spine plasticity and synaptic function in mature cultured hippocampal neurons. . J Cell Sci 122:, 524–534. [CrossRef] [PubMed]
    [Google Scholar]
  20. Iwata M. , Komori S. , Unno T. , Minamoto N. , Ohashi H. . ( 1999; ). Modification of membrane currents in mouse neuroblastoma cells following infection with rabies virus. . Br J Pharmacol 126:, 1691–1698. [CrossRef] [PubMed]
    [Google Scholar]
  21. Kasai H. , Fukuda M. , Watanabe S. , Hayashi-Takagi A. , Noguchi J. . ( 2010; ). Structural dynamics of dendritic spines in memory and cognition. . Trends Neurosci 33:, 121–129. [CrossRef] [PubMed]
    [Google Scholar]
  22. Kiuchi T. , Ohashi K. , Kurita S. , Mizuno K. . ( 2007; ). Cofilin promotes stimulus-induced lamellipodium formation by generating an abundant supply of actin monomers. . J Cell Biol 177:, 465–476. [CrossRef] [PubMed]
    [Google Scholar]
  23. Kuriu T. , Inoue A. , Bito H. , Sobue K. , Okabe S. . ( 2006; ). Differential control of postsynaptic density scaffolds via actin-dependent and -independent mechanisms. . J Neurosci 26:, 7693–7706. [CrossRef] [PubMed]
    [Google Scholar]
  24. Laothamatas J. , Wacharapluesadee S. , Lumlertdacha B. , Ampawong S. , Tepsumethanon V. , Shuangshoti S. , Phumesin P. , Asavaphatiboon S. , Worapruekjaru L. . & other authors ( 2008; ). Furious and paralytic rabies of canine origin: neuroimaging with virological and cytokine studies. . J Neurovirol 14:, 119–129. [CrossRef] [PubMed]
    [Google Scholar]
  25. Law A. J. , Weickert C. S. , Hyde T. M. , Kleinman J. E. , Harrison P. J. . ( 2004; ). Reduced spinophilin but not microtubule-associated protein 2 expression in the hippocampal formation in schizophrenia and mood disorders: molecular evidence for a pathology of dendritic spines. . Am J Psychiatry 161:, 1848–1855. [CrossRef] [PubMed]
    [Google Scholar]
  26. Li X. Q. , Sarmento L. , Fu Z. F. . ( 2005; ). Degeneration of neuronal processes after infection with pathogenic, but not attenuated, rabies viruses. . J Virol 79:, 10063–10068. [CrossRef] [PubMed]
    [Google Scholar]
  27. Li Y. C. , Bai W. Z. , Hashikawa T. . ( 2007; ). Regionally varying F-actin network in the apical cytoplasm of ependymocytes. . Neurosci Res 57:, 522–530. [CrossRef] [PubMed]
    [Google Scholar]
  28. Lisman J. , Schulman H. , Cline H. . ( 2002; ). The molecular basis of CaMKII function in synaptic and behavioural memory. . Nat Rev Neurosci 3:, 175–190. [CrossRef] [PubMed]
    [Google Scholar]
  29. Matus A. , Brinkhaus H. , Wagner U. . ( 2000; ). Actin dynamics in dendritic spines: a form of regulated plasticity at excitatory synapses. . Hippocampus 10:, 555–560. [CrossRef] [PubMed]
    [Google Scholar]
  30. Nag S. , Ma Q. , Wang H. , Chumnarnsilpa S. , Lee W. L. , Larsson M. , Kannan B. , Hernandez-Valladares M. , Burtnick L. D. , Robinson R. C. . ( 2009; ). Ca2+ binding by domain 2 plays a critical role in the activation and stabilization of gelsolin. . Proc Natl Acad Sci U S A 106:, 13713–13718. [CrossRef] [PubMed]
    [Google Scholar]
  31. Ouyang Y. , Wong M. , Capani F. , Rensing N. , Lee C. S. , Liu Q. , Neusch C. , Martone M. E. , Wu J. Y. . & other authors ( 2005; ). Transient decrease in F-actin may be necessary for translocation of proteins into dendritic spines. . Eur J Neurosci 22:, 2995–3005. [CrossRef] [PubMed]
    [Google Scholar]
  32. Ouyang Y. , Yang X. F. , Hu X. Y. , Erbayat-Altay E. , Zeng L. H. , Lee J. M. , Wong M. . ( 2007; ). Hippocampal seizures cause depolymerization of filamentous actin in neurons independent of acute morphological changes. . Brain Res 1143:, 238–246. [CrossRef] [PubMed]
    [Google Scholar]
  33. Renner M. , Choquet D. , Triller A. . ( 2009; ). Control of the postsynaptic membrane viscosity. . J Neurosci 29:, 2926–2937. [CrossRef] [PubMed]
    [Google Scholar]
  34. Scott C. A. , Rossiter J. P. , Andrew R. D. , Jackson A. C. . ( 2008; ). Structural abnormalities in neurons are sufficient to explain the clinical disease and fatal outcome of experimental rabies in yellow fluorescent protein-expressing transgenic mice. . J Virol 82:, 513–521. [CrossRef] [PubMed]
    [Google Scholar]
  35. Sheng M. . ( 2001; ). Molecular organization of the postsynaptic specialization. . Proc Natl Acad Sci U S A 98:, 7058–7061. [CrossRef] [PubMed]
    [Google Scholar]
  36. Shi Y. , Ethell I. M. . ( 2006; ). Integrins control dendritic spine plasticity in hippocampal neurons through NMDA receptor and Ca2+/calmodulin-dependent protein kinase II-mediated actin reorganization. . J Neurosci 26:, 1813–1822. [CrossRef] [PubMed]
    [Google Scholar]
  37. Stein L. T. , Rech R. R. , Harrison L. , Brown C. C. . ( 2010; ). Immunohistochemical study of rabies virus within the central nervous system of domestic and wildlife species. . Vet Pathol 47:, 630–633. [CrossRef] [PubMed]
    [Google Scholar]
  38. Torres-Fernández O. , Yepes G. E. , Gómez J. E. . ( 2007; ). Neuronal dentritic morphology alterations in the cerebral cortex of rabies-infected mice: a Golgi study. . Biomedica 27:, 605–613 (in Spanish).[PubMed] [CrossRef]
    [Google Scholar]
  39. Tsiang H. . ( 1993; ). Pathophysiology of rabies virus infection of the nervous system. . Adv Virus Res 42:, 375–412. [CrossRef] [PubMed]
    [Google Scholar]
  40. Valtorta F. , Benfenati F. , Greengard P. . ( 1992; ). Structure and function of the synapsins. . J Biol Chem 267:, 7195–7198.[PubMed]
    [Google Scholar]
  41. Xiang Y. , Zheng K. , Ju H. , Wang S. , Pei Y. , Ding W. , Chen Z. , Wang Q. , Qiu X. . & other authors ( 2012; ). Cofilin 1-mediated biphasic F-actin dynamics of neuronal cells affect herpes simplex virus 1 infection and replication. . J Virol 86:, 8440–8451. [CrossRef] [PubMed]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.047480-0
Loading
/content/journal/jgv/10.1099/vir.0.047480-0
Loading

Data & Media loading...

Most Cited This Month

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error