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Nat Med. 1996 Sep;2(9):1017-21.

Inhibition of neuronal nitric oxide synthase prevents MPTP-induced parkinsonism in baboons.

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1
Unité de Recherche Associé Commissariat á l'Energie Atomique, Centre National de la Recherche Scientifique 2210, Service Hospitalier Frederic Joliot, Orsay, France.

Abstract

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) produces clinical, biochemical and neuropathologic changes reminiscent of those which occur in idiopathic Parkinson's disease. 7-Nitroindazole (7-NI) is a relatively selective inhibitor of the neuronal isoform of nitric oxide synthase (NOS) that blocks MPTP neurotoxicity in mice. We now show that 7-NI protects against profound striatal dopamine depletions and loss of tyrosine hydroxylase-positive neurons in the substantia nigra in MPTP-treated baboons. Furthermore, 7-NI protected against MPTP-induced motor and frontal-type cognitive deficits. These results strongly implicate a role of nitric oxide in MPTP neurotoxicity and suggest that inhibitors of neuronal NOS might be useful in treating Parkinson's disease.

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PMID:
8782460
DOI:
10.1038/nm0996-1017
[Indexed for MEDLINE]

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