Protective effects of neuronal nitric oxide synthase inhibitor in mouse brain against MPTP neurotoxicity: An immunohistological study

Hijiri Watanabe, Yasuko Muramatsu, Rumiko Kurosaki, Mari Michimata, Mitsunobu Matsubara, Yutaka Imai, Tsutomu Araki

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61 Citations (Scopus)


We recently reported that neuronal nitric oxide synthase (nNOS) inhibitor, 7-nitroindazole, can protect against 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine (MPTP) neurotoxicity in mice. It protected against both dopamine depletions and tyrosine hydroxylase (TH) positive neuron decreases in the mouse brain. In the present study, we further examined whether 7-nitroindazole can also protect against the alterations of TH-, microtubule-associated protein 2a,b (MAP2)-, glial fibrillary acidic protein (GFAP)-, parvalbumin (PV)-, dopamine transporter (DAT)-, nNOS- or endothelial NOS (eNOS)-positive cells, in comparison with pargyline as a relatively selective inhibitor of the monoamine oxidase-B (MAO-B). The present study showed that nNOS inhibitor as well as MAO-B inhibitor has a dose-dependent protective effect against MPTP-induced striatal dopamine and DOPAC depletion in mice. Furthermore, the present study revealed that 7-nitroindazole and pargyline can protect the alterations of immunohistochemical changes in the striatum and substantia nigra after MPTP treatment. These protective effects may be, at least in part, produced by the reduction of neuronally derived NO and peroxynitrite caused by MPTP. Our results also demonstrate that MPTP can cause functional damage of interneurons in the substantia nigra. These results suggest the possibility that nNOS inhibitors as well as MAO-B inhibitors may be therapeutically useful in neurodegenerative diseases such as Parkinson's disease. Thus our present results provide valuable information for the pathogenesis of degeneration of the nigrostriatal dopaminergic neuronal pathway.

Original languageEnglish
Pages (from-to)93-104
Number of pages12
JournalEuropean Neuropsychopharmacology
Issue number2
Publication statusPublished - 2004 Mar


  • Dopamine content
  • Immunohistochemistry
  • MPTP
  • Mice
  • Monoamine oxidase-B (MAO-B) inhibitor
  • Neuronal nitric oxide synthase (nNOS) inhibitor

ASJC Scopus subject areas

  • Pharmacology
  • Neurology
  • Clinical Neurology
  • Psychiatry and Mental health
  • Biological Psychiatry
  • Pharmacology (medical)


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