Therapeutic effect of neuronal nitric oxide synthase inhibitor (7-nitroindazole) against MPTP neurotoxicity in mice

Y. Muramatsu, R. Kurosaki, T. Mikami, M. Michimata, M. Matsubara, Y. Imai, H. Kato, Y. Itoyama, T. Araki

Research output: Contribution to journalArticlepeer-review

38 Citations (Scopus)

Abstract

Effects of neuronal nitric oxide synthase (nNOS) inhibitor (7-nitroindazole), nonselective NOS inhibitor (NG-nitro-L-arginine methyl ester; L-NAME), and monoamine oxidase inhibitor (pargyline) were studied on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice. The mice received four intraperitoneal injections of MPTP at 1-h intervals. A significant depletion in dopamine and DOPAC concentration was observed in the striatum from 1 day after MPTP treatment. The pretreatment of 7-nitroindazole and pargyline, but not L-NAME, dose-dependently protected against MPTP-induced depletion in dopamine content 3 days after MPTP treatment. Our histochemical study also showed that 7-nitroindazole and pargyline can prevent a marked decrease in the nigral cells and a marked increase in astrocytes in striatum 7 days after MPTP treatment. The protective effect of 7-nitroindazole against MPTP-induced dopamine and DOPAC depletion in the striatum was not attenuated by intraperitoneal pretreatment with L-arginine. Furthermore, the posttreatment of 7-nitroindazole or pargyline protected against MPTP-induced depletion of dopamine content. These results demonstrate that the protective mechanism by which 7-nitroindazole counteracts MPTP neurotoxicity in mice may be due not only to inhibition of nNOS, but also to MAO-B inhibition. Furthermore, our study suggests that the posttreatment of 7-nitroindazole and pargyline can prevent a significant decrease in dopamine levels in the striatum of MPTP-treated mice. These findings have important implications for the therapeutic time window and choice of nNOS or MAO inhibitors in patients with Parkinson's disease.

Original languageEnglish
Pages (from-to)169-182
Number of pages14
JournalMetabolic Brain Disease
Volume17
Issue number3
DOIs
Publication statusPublished - 2002 Sep 1

Keywords

  • 7-nitroindazole
  • Dopamine
  • Immunohistochemistry
  • L-NAME
  • MPTP
  • Mice
  • Pargyline

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Neurology
  • Cellular and Molecular Neuroscience

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