Protective effect of a novel free radical scavenger, OPC-14117, on wobbler mouse motor neuron disease

K. Abe, S. Morita, T. Kikuchi, Y. Itoyama

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

A possible protective effect of a novel free radical scavenger, OPC- 14117, on the progressive motor neuron death in wobbler mice was examined. Clinical parameters such as mortality, body weight, motor activity as a rolling number of circular cage, and forelimb muscle power as grasping on a rolling column, an angle of slipping down from slope, and hanging ability on a flat plate were compared every 4 weeks from 4 to 36 weeks of age among mice groups treated with vehicle or daily oral administration of OPC-14117 of 10 or 30 mg/kg body weight. The treatment with OPC-14117 dose dependently improved the clinical parameters such as mortality, motor activity, and forelimb weakness. Pathological analysis showed that a diffuse neurogenic change in the forelimb muscle was improved at 36 weeks of age in the drug treated mice with a marked preservation of motor neurons in the spinal cord. Treatment of the mice with the drug reduced age-dependent increase of lipid peroxides in the spinal cord in vivo, and a supplement of the drug to the homogenate of spinal cord in vitro ameliorated the formations of lipid peroxides generated by an exogenous addition of ascorbate or xanthine/xanthine oxidase. These results suggest that OPC-14117 has a protective effect on the motor neuron death probably as a free radical scavenger, resulting in an improvement of clinical symptoms in wobber mice.

Original languageEnglish
Pages (from-to)63-70
Number of pages8
JournalJournal of Neuroscience Research
Volume48
Issue number1
DOIs
Publication statusPublished - Apr 1 1997
Externally publishedYes

Keywords

  • OPC-14117
  • free radical
  • motor neuron death
  • wobbler mice

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

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