MovDisordV3, France, Analysis, bibRecord, 000420

In vivo models of multiple system atrophy

Identifieur interne : 000420 ( France/Analysis ); précédent : 000419; suivant : 000421

In vivo models of multiple system atrophy

Auteurs : Pierre-Olivier Femagut [États-Unis] ; Imad Ghorayeb [France] ; Elsa Diguet [France] ; Francois Tison [France]

Source :

Movement disorders [ 0885-3185 ] ; 2005.

RBID : Pascal:05-0457468

Descripteurs français

Pascal (Inist)
- Système nerveux pathologie, Atrophie multisystématisée, Parkinsonisme, Modèle, Lévodopa, Physiopathologie.

English descriptors

KwdEn :
- Levodopa, Models, Multiple system atrophy, Nervous system diseases, Parkinsonism, Pathophysiology.

Abstract

Multiple system atrophy (MSA) is a sporadic adult-onset neurodegenerative disorder of unknown etiology clinically characterized by a combination of parkinsonian, pyramidal, and cerebellar signs. Levodopa-unresponsive parkinsonism is present in 80% of MSA cases, and this dominant clinical presentation (MSA-P) is associated with a combined degeneration of the substantia nigra pars compacta and the striatum in anatomically related areas. The limited knowledge of the pathophysiology of MSA and the lack of therapeutic strategies prompted the development of lesion models reproducing striatonigral degeneration, the substrate of levodopa-unresponsive parkinsonism in MSA-P. This method was carried out first in rats with two different stereotaxic strategies using either two neurotoxins ("double toxin-double lesion") or a single neuro-toxin ("single toxin-double lesion"). Double-lesioned rat models showed severe motor impairment compared to those with a single nigral or striatal lesion and helped to mimic different stages of the disease. Systemic models were also developed in mice and primates using the nigral toxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and the striatal toxin 3-nitropropionic (3-NP). In mice, although MPTP reduced the subsequent sensitivity to 3-NP in a sequential lesion, simultaneous nigral and striatal insults were shown to exacerbate striatal damage. MPTP-treated monkeys displayed a significant worsening of parkinsonism and a loss of levodopa-responsiveness after the appearance of hindlimb dystonia and striatal lesion formation induced by subsequent 3-NP intoxication. The different species and intoxication paradigms used will be useful to investigate functional changes in substantia nigra and striatum and to define neuroprotective, neurorestorative, or symptomatic therapeutic strategies.

Affiliations:

Links toward previous steps (curation, corpus...)

to stream PascalFrancis, to step Corpus: 001D78
to stream PascalFrancis, to step Curation: 000F43
to stream PascalFrancis, to step Checkpoint: 001E21
to stream Main, to step Merge: 005299
to stream Main, to step Curation: 003A68
to stream Main, to step Exploration: 003A68
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Links to Exploration step

Pascal:05-0457468

Le document en format XML

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<front><div type="abstract" xml:lang="en">Multiple system atrophy (MSA) is a sporadic adult-onset neurodegenerative disorder of unknown etiology clinically characterized by a combination of parkinsonian, pyramidal, and cerebellar signs. Levodopa-unresponsive parkinsonism is present in 80% of MSA cases, and this dominant clinical presentation (MSA-P) is associated with a combined degeneration of the substantia nigra pars compacta and the striatum in anatomically related areas. The limited knowledge of the pathophysiology of MSA and the lack of therapeutic strategies prompted the development of lesion models reproducing striatonigral degeneration, the substrate of levodopa-unresponsive parkinsonism in MSA-P. This method was carried out first in rats with two different stereotaxic strategies using either two neurotoxins ("double toxin-double lesion") or a single neuro-toxin ("single toxin-double lesion"). Double-lesioned rat models showed severe motor impairment compared to those with a single nigral or striatal lesion and helped to mimic different stages of the disease. Systemic models were also developed in mice and primates using the nigral toxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and the striatal toxin 3-nitropropionic (3-NP). In mice, although MPTP reduced the subsequent sensitivity to 3-NP in a sequential lesion, simultaneous nigral and striatal insults were shown to exacerbate striatal damage. MPTP-treated monkeys displayed a significant worsening of parkinsonism and a loss of levodopa-responsiveness after the appearance of hindlimb dystonia and striatal lesion formation induced by subsequent 3-NP intoxication. The different species and intoxication paradigms used will be useful to investigate functional changes in substantia nigra and striatum and to define neuroprotective, neurorestorative, or symptomatic therapeutic strategies.</div>
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	Movement Disorders (revue)
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Movement Disorders (revue)

In vivo models of multiple system atrophy

In vivo models of multiple system atrophy

Source :

Descripteurs français

English descriptors

Abstract

Links toward previous steps (curation, corpus...)

Links to Exploration step

Le document en format XML

Pour manipuler ce document sous Unix (Dilib)

Pour mettre un lien sur cette page dans le réseau Wicri