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

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.