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

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

Research output: Contribution to journalArticle

12 Citations (Scopus)

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 1988
Externally publishedYes

Fingerprint

Vinca Alkaloids
Axotomy
Ornithine Decarboxylase
Spinal Ganglia
Vinblastine
Axons
Axonal Transport
Poisons
Vincristine
Sciatic Nerve
Neurons
Repair
Communication

Keywords

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

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry

Cite this

Axotomy-induced ornithine decarboxylase activity in the mouse dorsal root ganglion is inhibited by the vinca alkaloids. / Soiefer, Andrew I.; Moretto, Angelo; Spencer, Peter; Sabri, Mohammad I.

In: Neurochemical Research, Vol. 13, No. 12, 12.1988, p. 1169-1173.

Research output: Contribution to journalArticle

Soiefer, Andrew I. ; Moretto, Angelo ; Spencer, Peter ; Sabri, Mohammad I. / Axotomy-induced ornithine decarboxylase activity in the mouse dorsal root ganglion is inhibited by the vinca alkaloids. In: Neurochemical Research. 1988 ; Vol. 13, No. 12. pp. 1169-1173.
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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.",
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