Axotomy-induced ornithine decarboxylase activity in the mouse dorsal root ganglion is inhibited by the vinca alkaloids

Andrew I. Soiefer, Angelo Moretto, Peter S. Spencer, Mohammad I. Sabri

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

Vinca alkaloids were used to study the role of retrograde axon transport (RT) in activating neuron perikaryal repair response to nerve transection. Mouse lumbar dorsal root ganglia (DRG) (L4-L6) were excised 48 hours after unilateral transection of the sciatic nerve and ornithine decarboxylase (ODC) activity determined. ODC activity in DRG ipsilateral to nerve transection was increased 10-20 fold over contralateral values. Typical ODC activities in ipsilateral and contralateral DRG samples were 6.18±1.4 and 0.31±0.09 pmol14CO2 released/h/3DRG, respectively. Systemic administration of single doses of either vincristine (1 mg/kg) or vinblastine (5 mg/kg) immediately prior to axotomy attenuated ODC induction in ipsilateral DRG by 39% and 47%, respectively. A direct inhibition of ODC activity in the DRG appears unlikely since only high concentrations of vinblastine (0.5-1.0 mM) were able to inhibit ODC activity in vitro. We suggest vinca alkaloids inhibit ODC induction as a consequence of distupting retrograde axonal transport. Interruption of this intracellular communication mechanism may be etiologically linked to the distal axon degeneration which follows repetitive exposure to vinca alkaloids and other agents that induce toxic axonal neuropathy.

Original languageEnglish (US)
Pages (from-to)1169-1173
Number of pages5
JournalNeurochemical Research
Volume13
Issue number12
DOIs
StatePublished - Dec 1 1988

Keywords

  • Vinca Alkaloids
  • axotomy
  • dorsal root ganglia
  • neurotoxicity
  • ornithine decarboxylase
  • retrograde axon transport

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Fingerprint Dive into the research topics of 'Axotomy-induced ornithine decarboxylase activity in the mouse dorsal root ganglion is inhibited by the vinca alkaloids'. Together they form a unique fingerprint.

  • Cite this