Impaired fast axonal transport in neurons of the sciatic nerves from dystonia musculorum mice

Authors

  • Yves De Repentigny,

    1. Ottawa Health Research Institute, Ottawa, Ontario, Canada
    2. The University of Ottawa Center for Neuromuscular Disease, Ottawa, Ontario, Canada
    Search for more papers by this author
    • 1

      These authors contributed equally to this work.

  • Julie Deschênes-Furry,

    1. The University of Ottawa Center for Neuromuscular Disease, Ottawa, Ontario, Canada
    2. Department of Cellular and Molecular Medicine and
    Search for more papers by this author
    • 1

      These authors contributed equally to this work.

  • Bernard J. Jasmin,

    1. Ottawa Health Research Institute, Ottawa, Ontario, Canada
    2. The University of Ottawa Center for Neuromuscular Disease, Ottawa, Ontario, Canada
    3. Department of Cellular and Molecular Medicine and
    Search for more papers by this author
  • Rashmi Kothary

    1. Ottawa Health Research Institute, Ottawa, Ontario, Canada
    2. The University of Ottawa Center for Neuromuscular Disease, Ottawa, Ontario, Canada
    3. Department of Cellular and Molecular Medicine and
    4. Department of Medicine, University of Ottawa, Ottawa, Ontario,Canada
    Search for more papers by this author

Address correspondence and reprint requests to Rashmi Kothary, Ottawa Health Research Institute, 501 Smyth Road, Ottawa, Ontario, Canada K1H 8L6. E-mail: rkothary@ohri.ca

Abstract

Dystonia musculorum (dt) mice suffer from a severe sensory neuropathy caused by mutations in the gene encoding the cytoskeletal cross-linker protein dystonin/bullous pemphigoid antigen 1 (Bpag1). Loss of function of dystonin/Bpag1 within neurons leads to a loss in the maintenance of cytoskeletal organization and to the development of focal axonal swellings prior to death of the neuron. In the present study, we demonstrate that neurons within the sciatic nerves of dt27J mice undergo axonal degeneration as has been previously reported for the dorsal roots. Furthermore, ultrastructural studies reveal a perturbed organization of the neurofilament and microtubule networks within the axons of sciatic nerves in dt27J mice. The disrupted cytoskeletal organization suggested that axonal transport is affected in dt mice. To address this, we assessed fast axonal transport by measuring the rate of accumulation of acetylcholinesterase (AChE) proximal and distal to a surgically introduced ligature on the sciatic nerves of normal and dt27J mice. Our findings demonstrate that axonal transport of AChE in both orthograde and retrograde directions is markedly affected, and allow us to conclude that axonal transport defects do exist in the sciatic nerves of dt27J mice.

Ancillary