Immunohistochemical and transcriptome analyses indicate complex breakdown of axonal transport mechanisms in canine distemper leukoencephalitis

Brain Behav. 2016 May 3;6(7):e00472. doi: 10.1002/brb3.472. eCollection 2016 Jul.


Introduction: CDV-DL (Canine distemper virus-induced demyelinating leukoencephalitis) represents a spontaneously occurring animal model for demyelinating disorders. Axonopathy represents a key pathomechanism in this disease; however, its underlying pathogenesis has not been addressed in detail so far. This study aimed at the characterization of axonal cytoskeletal, transport, and potential regenerative changes with a parallel focus upon Schwann cell remyelination.

Methods: Immunohistochemistry of canine cerebellar tissue as well as a comparative analysis of genes from an independent microarray study were performed.

Results: Increased axonal immunoreactivity for nonphosphorylated neurofilament was followed by loss of cytoskeletal and motor proteins. Interestingly, a subset of genes encoding for neurofilament subunits and motor proteins was up-regulated in the chronic stage compared to dogs with subacute CDV-DL. However, immunohistochemically, hints for axonal regeneration were restricted to up-regulated axonal positivity of hypoxia-inducible factor 1 alpha, while growth-associated protein 43, erythropoietin and its receptor were not or even down-regulated. Periaxin-positive structures, indicative of Schwann cell remyelination, were only detected within few advanced lesions.

Conclusions: The present findings demonstrate a complex sequence of axonal cytoskeletal breakdown mechanisms. Moreover, though sparse, this is the first report of Schwann cell remyelination in CDV-DL. Facilitation of these very limited endogenous regenerative responses represents an important topic for future research.

Keywords: Growth‐associated protein 43; Schwann cell; microarray; neurofilament; p75 neurotrophin receptor; periaxin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Axonal Transport / physiology*
  • Case-Control Studies
  • Distemper / genetics*
  • Distemper / metabolism*
  • Distemper / pathology
  • Distemper Virus, Canine / isolation & purification
  • Dogs
  • Female
  • Immunohistochemistry
  • Leukoencephalopathies / genetics
  • Leukoencephalopathies / metabolism
  • Leukoencephalopathies / veterinary*
  • Leukoencephalopathies / virology
  • Male
  • Nerve Fibers, Myelinated / pathology
  • Nerve Regeneration / physiology
  • Retrospective Studies
  • Schwann Cells / pathology
  • Transcriptome