title: Immunohistochemical and transcriptome analyses indicate complex breakdown of axonal transport mechanisms in canine distemper leukoencephalitis.
abstract: 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.
  
  
  
  Immunohistochemistry of canine cerebellar tissue as well as a comparative analysis of genes from an independent microarray study were performed.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Department of Pathology University of Veterinary Medicine Hannover Foundation Bünteweg 17 30559 Hannover Germany; Center for Systems Neuroscience Bünteweg 2 30559 Hannover Germany.
authors.forename: Ingo
authors.initials: I
authors.lastname: Spitzbarth
authors.affiliation: Department of Pathology University of Veterinary Medicine Hannover Foundation Bünteweg 17 30559 Hannover Germany.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Lempp
authors.affiliation: Department of Pathology University of Veterinary Medicine Hannover Foundation Bünteweg 17 30559 Hannover Germany; Center for Systems Neuroscience Bünteweg 2 30559 Hannover Germany.
authors.forename: Kristel
authors.initials: K
authors.lastname: Kegler
authors.affiliation: Department of Pathology University of Veterinary Medicine Hannover Foundation Bünteweg 17 30559 Hannover Germany; Center for Systems Neuroscience Bünteweg 2 30559 Hannover Germany.
authors.forename: Reiner
authors.initials: R
authors.lastname: Ulrich
authors.affiliation: Department of Non-Clinical Drug Safety Boehringer Ingelheim Pharma GmbH & Co KG Biberach (Riß) Germany.
authors.forename: Arno
authors.initials: A
authors.lastname: Kalkuhl
authors.affiliation: Department of Non-Clinical Drug Safety Boehringer Ingelheim Pharma GmbH & Co KG Biberach (Riß) Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Deschl
authors.affiliation: Department of Pathology University of Veterinary Medicine Hannover Foundation Bünteweg 17 30559 Hannover Germany; Center for Systems Neuroscience Bünteweg 2 30559 Hannover Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Baumgärtner
authors.affiliation: Department of Pathology University of Veterinary Medicine Hannover Foundation Bünteweg 17 30559 Hannover Germany.
authors.forename: Frauke
authors.initials: F
authors.lastname: Seehusen
mesh_terms: D000818:Animals; D001370:Axonal Transport / Q000502:physiology*; D016022:Case-Control Studies; D004216:Distemper / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D004217:Distemper Virus, Canine / Q000302:isolation & purification; D004285:Dogs; D005260:Female; D007150:Immunohistochemistry; D056784:Leukoencephalopathies / Q000235:genetics / Q000378:metabolism / Q000662:veterinary* / Q000821:virology; D008297:Male; D009413:Nerve Fibers, Myelinated / Q000473:pathology; D009416:Nerve Regeneration / Q000502:physiology; D012189:Retrospective Studies; D012583:Schwann Cells / Q000473:pathology; D059467:Transcriptome
keywords: Growth‐associated protein 43; Schwann cell; microarray; neurofilament; p75 neurotrophin receptor; periaxin