Inhibition of neuronal nitric oxide synthase prevents MPTP-induced parkinsonism in baboons.
Identifieur interne : 004478 ( Main/Exploration ); précédent : 004477; suivant : 004479Inhibition of neuronal nitric oxide synthase prevents MPTP-induced parkinsonism in baboons.
Auteurs : P. Hantraye [France] ; E. Brouillet ; R. Ferrante ; S. Palfi ; R. Dolan ; R T Matthews ; M F BealSource :
- Nature medicine [ 1078-8956 ] ; 1996.
English descriptors
- KwdEn :
- 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine, 3,4-Dihydroxyphenylacetic Acid (metabolism), Animals, Disease Models, Animal, Dopamine (metabolism), Enzyme Inhibitors (pharmacology), Homovanillic Acid (metabolism), Hypokinesia, Indazoles (pharmacology), Male, Motor Activity, Neurologic Examination, Neurons (drug effects), Neurons (enzymology), Nitric Oxide Synthase (antagonists & inhibitors), Nitric Oxide Synthase (metabolism), Papio, Parkinson Disease, Secondary (chemically induced), Parkinson Disease, Secondary (drug therapy), Parkinson Disease, Secondary (enzymology), Substantia Nigra (drug effects), Substantia Nigra (enzymology), Videotape Recording.
- MESH :
- chemical , antagonists & inhibitors : Nitric Oxide Synthase.
- chemical , metabolism : 3,4-Dihydroxyphenylacetic Acid, Dopamine, Homovanillic Acid, Nitric Oxide Synthase.
- chemical , pharmacology : Enzyme Inhibitors, Indazoles.
- chemical : 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine.
- chemically induced : Parkinson Disease, Secondary.
- drug effects : Neurons, Substantia Nigra.
- drug therapy : Parkinson Disease, Secondary.
- enzymology : Neurons, Parkinson Disease, Secondary, Substantia Nigra.
- Animals, Disease Models, Animal, Hypokinesia, Male, Motor Activity, Neurologic Examination, Papio, Videotape Recording.
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.
PubMed: 8782460
Affiliations:
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Le document en format XML
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Brouillet</name></author><author><name sortKey="Ferrante, R" sort="Ferrante, R" uniqKey="Ferrante R" first="R" last="Ferrante">R. Ferrante</name></author><author><name sortKey="Palfi, S" sort="Palfi, S" uniqKey="Palfi S" first="S" last="Palfi">S. Palfi</name></author><author><name sortKey="Dolan, R" sort="Dolan, R" uniqKey="Dolan R" first="R" last="Dolan">R. Dolan</name></author><author><name sortKey="Matthews, R T" sort="Matthews, R T" uniqKey="Matthews R" first="R T" last="Matthews">R T Matthews</name></author><author><name sortKey="Beal, M F" sort="Beal, M F" uniqKey="Beal M" first="M F" last="Beal">M F Beal</name></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="1996">1996</date><idno type="RBID">pubmed:8782460</idno><idno type="pmid">8782460</idno><idno type="wicri:Area/PubMed/Corpus">001568</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">001568</idno><idno type="wicri:Area/PubMed/Curation">001527</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">001527</idno><idno type="wicri:Area/PubMed/Checkpoint">001527</idno><idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">001527</idno><idno type="wicri:Area/Ncbi/Merge">001E17</idno><idno type="wicri:Area/Ncbi/Curation">001E17</idno><idno type="wicri:Area/Ncbi/Checkpoint">001E17</idno><idno type="wicri:doubleKey">1078-8956:1996:Hantraye P:inhibition:of:neuronal</idno><idno type="wicri:Area/Main/Merge">004D35</idno><idno type="wicri:Area/Main/Curation">004478</idno><idno type="wicri:Area/Main/Exploration">004478</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Inhibition of neuronal nitric oxide synthase prevents MPTP-induced parkinsonism in baboons.</title><author><name sortKey="Hantraye, P" sort="Hantraye, P" uniqKey="Hantraye P" first="P" last="Hantraye">P. Hantraye</name><affiliation wicri:level="3"><nlm:affiliation>Unité de Recherche Associé Commissariat á l'Energie Atomique, Centre National de la Recherche Scientifique 2210, Service Hospitalier Frederic Joliot, Orsay, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Unité de Recherche Associé Commissariat á l'Energie Atomique, Centre National de la Recherche Scientifique 2210, Service Hospitalier Frederic Joliot, Orsay</wicri:regionArea><placeName><settlement type="city">Orsay</settlement></placeName></affiliation></author><author><name sortKey="Brouillet, E" sort="Brouillet, E" uniqKey="Brouillet E" first="E" last="Brouillet">E. Brouillet</name></author><author><name sortKey="Ferrante, R" sort="Ferrante, R" uniqKey="Ferrante R" first="R" last="Ferrante">R. Ferrante</name></author><author><name sortKey="Palfi, S" sort="Palfi, S" uniqKey="Palfi S" first="S" last="Palfi">S. Palfi</name></author><author><name sortKey="Dolan, R" sort="Dolan, R" uniqKey="Dolan R" first="R" last="Dolan">R. Dolan</name></author><author><name sortKey="Matthews, R T" sort="Matthews, R T" uniqKey="Matthews R" first="R T" last="Matthews">R T Matthews</name></author><author><name sortKey="Beal, M F" sort="Beal, M F" uniqKey="Beal M" first="M F" last="Beal">M F Beal</name></author></analytic><series><title level="j">Nature medicine</title><idno type="ISSN">1078-8956</idno><imprint><date when="1996" type="published">1996</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine</term><term>3,4-Dihydroxyphenylacetic Acid (metabolism)</term><term>Animals</term><term>Disease Models, Animal</term><term>Dopamine (metabolism)</term><term>Enzyme Inhibitors (pharmacology)</term><term>Homovanillic Acid (metabolism)</term><term>Hypokinesia</term><term>Indazoles (pharmacology)</term><term>Male</term><term>Motor Activity</term><term>Neurologic Examination</term><term>Neurons (drug effects)</term><term>Neurons (enzymology)</term><term>Nitric Oxide Synthase (antagonists & inhibitors)</term><term>Nitric Oxide Synthase (metabolism)</term><term>Papio</term><term>Parkinson Disease, Secondary (chemically induced)</term><term>Parkinson Disease, Secondary (drug therapy)</term><term>Parkinson Disease, Secondary (enzymology)</term><term>Substantia Nigra (drug effects)</term><term>Substantia Nigra (enzymology)</term><term>Videotape Recording</term></keywords><keywords scheme="MESH" type="chemical" qualifier="antagonists & inhibitors" xml:lang="en"><term>Nitric Oxide Synthase</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>3,4-Dihydroxyphenylacetic Acid</term><term>Dopamine</term><term>Homovanillic Acid</term><term>Nitric Oxide Synthase</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Enzyme Inhibitors</term><term>Indazoles</term></keywords><keywords scheme="MESH" type="chemical" xml:lang="en"><term>1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine</term></keywords><keywords scheme="MESH" qualifier="chemically induced" xml:lang="en"><term>Parkinson Disease, Secondary</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Neurons</term><term>Substantia Nigra</term></keywords><keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Parkinson Disease, Secondary</term></keywords><keywords scheme="MESH" qualifier="enzymology" xml:lang="en"><term>Neurons</term><term>Parkinson Disease, Secondary</term><term>Substantia Nigra</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Disease Models, Animal</term><term>Hypokinesia</term><term>Male</term><term>Motor Activity</term><term>Neurologic Examination</term><term>Papio</term><term>Videotape Recording</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">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.</div></front></TEI><affiliations><list><country><li>France</li></country><settlement><li>Orsay</li></settlement></list><tree><noCountry><name sortKey="Beal, M F" sort="Beal, M F" uniqKey="Beal M" first="M F" last="Beal">M F Beal</name><name sortKey="Brouillet, E" sort="Brouillet, E" uniqKey="Brouillet E" first="E" last="Brouillet">E. Brouillet</name><name sortKey="Dolan, R" sort="Dolan, R" uniqKey="Dolan R" first="R" last="Dolan">R. Dolan</name><name sortKey="Ferrante, R" sort="Ferrante, R" uniqKey="Ferrante R" first="R" last="Ferrante">R. Ferrante</name><name sortKey="Matthews, R T" sort="Matthews, R T" uniqKey="Matthews R" first="R T" last="Matthews">R T Matthews</name><name sortKey="Palfi, S" sort="Palfi, S" uniqKey="Palfi S" first="S" last="Palfi">S. Palfi</name></noCountry><country name="France"><noRegion><name sortKey="Hantraye, P" sort="Hantraye, P" uniqKey="Hantraye P" first="P" last="Hantraye">P. Hantraye</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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