Inhibition of neuronal nitric oxide synthase prevents MPTP–induced parkinsonism in baboons
P Hantraye, E Brouillet, R Ferrante, S Palfi, R Dolan… - Nature medicine, 1996 - nature.com
Nature medicine, 1996•nature.com
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 …
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 …
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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