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Impaired fast axonal transport in neurons of the sciatic nerves from dystonia musculorum mice
Author(s) -
De Repentigny Yves,
DeschênesFurry Julie,
Jasmin Bernard J.,
Kothary Rashmi
Publication year - 2003
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2003.01861.x
Subject(s) - axoplasmic transport , sciatic nerve , neurofilament , cytoskeleton , neuroscience , biology , anatomy , microtubule , neurite , pathology , microbiology and biotechnology , medicine , immunohistochemistry , biochemistry , genetics , cell , in vitro
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 dt 27J 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 dt 27J 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 dt 27J 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 dt 27J mice.