Toward a primate model of l-dopa-unresponsive parkinsonism mimicking striatonigral degeneration

We developed a primate model of striatonigral degeneration (SND), the neuropathology underlying levodopa‐unresponsive parkinsonism associated with multiple systemic atrophy (MSA‐P), by sequential systemic administration of 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP) and 3‐nitropropionic acid...

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Vydáno v:	Movement disorders Ročník 15; číslo 3; s. 531 - 536
Hlavní autoři:	Ghorayeb, Imad, Fernagut, Pierre O., Aubert, Incarnation, Bezard, Erwan, Poewe, Werner, Wenning, Gregor K., Tison, François
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	New York John Wiley & Sons, Inc 01.05.2000 Wiley
Témata:	1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine Animals Antiparkinson Agents - pharmacology Biological and medical sciences Brain Mapping Corpus Striatum - drug effects Corpus Striatum - pathology Corpus Striatum - physiopathology Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases Diagnosis, Differential Disease Models, Animal Dopamine - metabolism Levodopa - pharmacology Macaca fascicularis Male Medical sciences MPTP-3 nitropropionic acid Multiple system atrophy Multiple System Atrophy - chemically induced Multiple System Atrophy - pathology Multiple System Atrophy - physiopathology Nerve Degeneration - chemically induced Nerve Degeneration - pathology Nerve Degeneration - physiopathology Neurology Neurotoxins Nitro Compounds Parkinson Disease, Secondary - chemically induced Parkinson Disease, Secondary - pathology Parkinson Disease, Secondary - physiopathology Parkinsonism Primate model Primates Propionates Striatonigral degeneration Striatonigral Degeneration - chemically induced Striatonigral Degeneration - pathology Striatonigral Degeneration - physiopathology Animal model Nervous system diseases Pathophysiology Monkey Cerebral disorder Parkinsonism Vertebrata Mammalia Animal Central nervous system disease Primates Multiple system atrophy Degenerative disease Nigrostriatal pathway
ISSN:	0885-3185, 1531-8257
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Popis
Shrnutí:	We developed a primate model of striatonigral degeneration (SND), the neuropathology underlying levodopa‐unresponsive parkinsonism associated with multiple systemic atrophy (MSA‐P), by sequential systemic administration of 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP) and 3‐nitropropionic acid (3NP) in a Macaca fascicularis monkey. l‐Dopa‐responsive parkinsonian features emerged after MPTP injections. Subsequent chronic 3NP administration aggravated the motor symptoms and abolished the l‐dopa response. In vivo magnetic resonance imaging revealed bilateral striatal lesions. Histopathologically, there was severe dopaminergic cell loss in the substantia nigra pars compacta compared with the control monkey. Furthermore, we observed circumscribed areas of severe neuronal degeneration in the motor striatum. These changes were absent in the control monkey, and they were associated with diffuse metabolic failure as demonstrated by cytochrome oxidase histochemistry. The striatal pathology predominantly involved output pre‐pro‐enkephalin A‐ and substance P‐containing cells, whereas somatostatin (NADPH‐diaphorase)‐containing interneurons were relatively spared. Our model therefore reproduced levodopa‐unresponsive parkinsonism and SND‐like pathologic changes characteristic of MSA‐P. The double‐lesion primate model of SND may serve as a preclinical test‐bed for the evaluation of novel therapeutic strategies in MSA‐P.
Bibliografie:	ark:/67375/WNG-XR1N0RBW-3 Association France Parkinson, Institut Lilly, Conseil Général d'Aquitaine, Bundesministerium für Wissenschaft und Verkehr, Vienna - No. GZ 70038/2-Pr/4/98 istex:4D6E85DF3EC76EB51B1CC83F44AD782982A427DB ArticleID:MDS1017 ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0885-3185 1531-8257
DOI:	10.1002/1531-8257(200005)15:3<531::AID-MDS1017>3.0.CO;2-C