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

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.

journal_name

J Neurochem

authors

De Repentigny Y,Deschênes-Furry J,Jasmin BJ,Kothary R

doi

10.1046/j.1471-4159.2003.01861.x

keywords:

subject

Has Abstract

pub_date

2003-08-01 00:00:00

pages

564-71

issue

3

eissn

0022-3042

issn

1471-4159

pii

1861

journal_volume

86

pub_type

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