La maladie de Parkinson en France (serveur d'exploration)

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Intrastriatal injection of an adenoviral vector expressing glial-cell-line-derived neurotrophic factor prevents dopaminergic neuron degeneration and behavioral impairment in a rat model of Parkinson disease.

Identifieur interne : 001396 ( PubMed/Checkpoint ); précédent : 001395; suivant : 001397

Intrastriatal injection of an adenoviral vector expressing glial-cell-line-derived neurotrophic factor prevents dopaminergic neuron degeneration and behavioral impairment in a rat model of Parkinson disease.

Auteurs : A. Bilang-Bleuel [France] ; F. Revah ; P. Colin ; I. Locquet ; J J Robert ; J. Mallet ; P. Horellou

Source :

RBID : pubmed:9238061

English descriptors

Abstract

Glial-cell-line-derived neurotrophic factor (GDNF) is a potent neurotrophic factor for adult nigral dopamine neurons in vivo. GDNF has both protective and restorative effects on the nigro-striatal dopaminergic (DA) system in animal models of Parkinson disease. Appropriate administration of this factor is essential for the success of its clinical application. Since it cannot cross the blood-brain barrier, a gene transfer method may be appropriate for delivery of the trophic factor to DA cells. We have constructed a recombinant adenovirus (Ad) encoding GDNF and injected it into rat striatum to make use of its ability to infect neurons and to be retrogradely transported by DA neurons. Ad-GDNF was found to drive production of large amounts of GDNF, as quantified by ELISA. The GDNF produced after gene transfer was biologically active: it increased the survival and differentiation of DA neurons in vitro. To test the efficacy of the Ad-mediated GDNF gene transfer in vivo, we used a progressive lesion model of Parkinson disease. Rats received injections unilaterally into their striatum first of Ad and then 6 days later of 6-hydroxydopamine. We found that mesencephalic nigral dopamine neurons of animals treated with the Ad-GDNF were protected, whereas those of animals treated with the Ad-beta-galactosidase were not. This protection was associated with a difference in motor function: amphetamine-induced turning was much lower in animals that received the Ad-GDNF than in the animals that received Ad-beta-galactosidase. This finding may have implications for the development of a treatment for Parkinson disease based on the use of neurotrophic factors.

PubMed: 9238061


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pubmed:9238061

Le document en format XML

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<div type="abstract" xml:lang="en">Glial-cell-line-derived neurotrophic factor (GDNF) is a potent neurotrophic factor for adult nigral dopamine neurons in vivo. GDNF has both protective and restorative effects on the nigro-striatal dopaminergic (DA) system in animal models of Parkinson disease. Appropriate administration of this factor is essential for the success of its clinical application. Since it cannot cross the blood-brain barrier, a gene transfer method may be appropriate for delivery of the trophic factor to DA cells. We have constructed a recombinant adenovirus (Ad) encoding GDNF and injected it into rat striatum to make use of its ability to infect neurons and to be retrogradely transported by DA neurons. Ad-GDNF was found to drive production of large amounts of GDNF, as quantified by ELISA. The GDNF produced after gene transfer was biologically active: it increased the survival and differentiation of DA neurons in vitro. To test the efficacy of the Ad-mediated GDNF gene transfer in vivo, we used a progressive lesion model of Parkinson disease. Rats received injections unilaterally into their striatum first of Ad and then 6 days later of 6-hydroxydopamine. We found that mesencephalic nigral dopamine neurons of animals treated with the Ad-GDNF were protected, whereas those of animals treated with the Ad-beta-galactosidase were not. This protection was associated with a difference in motor function: amphetamine-induced turning was much lower in animals that received the Ad-GDNF than in the animals that received Ad-beta-galactosidase. This finding may have implications for the development of a treatment for Parkinson disease based on the use of neurotrophic factors.</div>
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<name sortKey="Locquet, I" sort="Locquet, I" uniqKey="Locquet I" first="I" last="Locquet">I. Locquet</name>
<name sortKey="Mallet, J" sort="Mallet, J" uniqKey="Mallet J" first="J" last="Mallet">J. Mallet</name>
<name sortKey="Revah, F" sort="Revah, F" uniqKey="Revah F" first="F" last="Revah">F. Revah</name>
<name sortKey="Robert, J J" sort="Robert, J J" uniqKey="Robert J" first="J J" last="Robert">J J Robert</name>
</noCountry>
<country name="France">
<region name="Île-de-France">
<name sortKey="Bilang Bleuel, A" sort="Bilang Bleuel, A" uniqKey="Bilang Bleuel A" first="A" last="Bilang-Bleuel">A. Bilang-Bleuel</name>
</region>
</country>
</tree>
</affiliations>
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