The gene for slow Wallerian degeneration (Wld(s)) is also protective against vincristine neuropathy.
Neurological diseases are frequently associated with axonal degeneration, which leads to dysfunction though separation of neurons from their targets. The mechanisms of axonal degeneration are largely unknown and in many cases are independent of those occurring within cell bodies in neurodegenerative disorders. The Wld(s) mouse mutant demonstrates the unique phenotype of resistance to axonal degeneration after axotomy (slow Wallerian degeneration), making it a powerful tool for studying mechanisms of axonal degeneration. We asked whether the Wld(s) mutation also provides resistance to axonal degeneration in a slowly progressing neuropathy. Using cultured dorsal root ganglion neurons we compared the course of axonal degeneration in response to exposure to the neurotoxin vincristine and found that Wld(s) neurites were relatively resistant to vincristine neuropathy. These findings suggest common pathophysiologic mechanisms between axotomy-induced Wallerian degeneration and toxic neuropathy. The implications are wide-ranging and are relevant to the pathophysiology of axonal degeneration seen in a wide spectrum of neurological diseases ranging from stroke and head trauma to spinal cord injury and peripheral neuropathy.
Wang
M
M
Department of Neurology, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
Wu
Y
Y
Culver
D G
DG
Glass
J D
JD
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000633:toxicity*; D001369:Axons / Q000187:drug effects / Q000473:pathology; D002478:Cells, Cultured; D004351:Drug Resistance / Q000235:genetics; D005727:Ganglia, Spinal / Q000187:drug effects / Q000473:pathology; D005796:Genes / Q000235:genetics*; D007091:Image Processing, Computer-Assisted; D051379:Mice; D008810:Mice, Inbred C57BL; D008818:Mice, Neurologic Mutants; D014750:Vincristine / Q000633:toxicity*; D014855:Wallerian Degeneration / Q000235:genetics*
D000972:Antineoplastic Agents, Phytogenic; D014750:Vincristine