Effects of Nigrostriatal Denervation and L‐Dopa Therapy on the GABAergic Neurons of the Striatum in MPTP‐treated Monkeys and Parkinson's Disease: An In Situ Hybridization Study of GAD67 mRNA
Identifieur interne : 002165 ( Istex/Curation ); précédent : 002164; suivant : 002166Effects of Nigrostriatal Denervation and L‐Dopa Therapy on the GABAergic Neurons of the Striatum in MPTP‐treated Monkeys and Parkinson's Disease: An In Situ Hybridization Study of GAD67 mRNA
Auteurs : R. Levy [France] ; M. T. Herrero [France, Espagne] ; M. Ruberg [France] ; J. Villares [France] ; B. Faucheux [France] ; J. Guridi [Espagne] ; J. Guillen [Espagne] ; M. R. Luquin [Espagne] ; F. Javoy-Agid [France] ; J. A. Obeso [Espagne] ; Y. Agid [France] ; E. C. Hirsch [France]Source :
- European Journal of Neuroscience [ 0953-816X ] ; 1995-06.
English descriptors
Abstract
The effects of nigrostriatal denervation and L‐dopa therapy on GABAergic neurons were analysed in patients with Parkinson's disease and in monkeys rendered parkinsonian by MPTP intoxication. The expression of the messenger RNA coding for the 67 kDa isoform of glutamic acid decarboxylase (GAD67 mRNA), studied by quantitative in situ hybridization, was used as an index of the GABAergic activity of the striatal neurons. A significant increase in GAD67 mRNA expression, generalized to all GABAergic neurons, was observed in MPTP‐treated monkeys compared to control monkeys in the putamen and caudate nucleus (+44 and +67% respectively), but not in the ventral striatum. L‐Dopa therapy significantly reduced GAD67 mRNA expression in the putamen and caudate nucleus to levels similar to those found in control monkeys. However, the return to normal of GAD67 mRNA expression was not homogeneous across all neurons since it was followed by an increase of labelling in one subpopulation of GABAergic neurons and a decrease in another. These data suggest that in MPTP‐treated monkeys the degeneration of nigrostriatal dopaminergic neurons results in a generalized increase in GABAergic activity in all the GABAergic neurons of the striatum, which is partially reversed by L‐dopa therapy. As the expression of GAD67 mRNA is less intense in the ventral than in the dorsal striatum, this increase in striatal GABAergic activity may be related to the severity of nigrostriatal denervation. In parkinsonian patients who had been chronically treated with L‐dopa, GAD67 mRNA expression was significantly decreased in all GABAergic neurons, in the caudate nucleus (by 44%), putamen (by 43.5%) and ventral striatum (by 26%). The opposite variation of GAD67 mRNA in patients with Parkinson's disease, compared with MPTP‐treated monkeys, might be explained by the combination of chronic nigrostriatal denervation and long‐term L‐dopa therapy.
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DOI: 10.1111/j.1460-9568.1995.tb01110.x
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Javoy-Agid</name><affiliation wicri:level="1"><mods:affiliation>INSERM U.289, Hôpital de la Salpêtrière, 75013 Paris, France</mods:affiliation><country xml:lang="fr">France</country><wicri:regionArea>INSERM U.289, Hôpital de la Salpêtrière, 75013 Paris</wicri:regionArea></affiliation></author><author><name sortKey="Obeso, J A" sort="Obeso, J A" uniqKey="Obeso J" first="J. A." last="Obeso">J. A. Obeso</name><affiliation wicri:level="1"><mods:affiliation>Experimental Neurology, University of Navarra, 31080 Pamplona, Spain</mods:affiliation><country xml:lang="fr">Espagne</country><wicri:regionArea>Experimental Neurology, University of Navarra, 31080 Pamplona</wicri:regionArea></affiliation></author><author><name sortKey="Agid, Y" sort="Agid, Y" uniqKey="Agid Y" first="Y." last="Agid">Y. Agid</name><affiliation wicri:level="1"><mods:affiliation>INSERM U.289, Hôpital de la Salpêtrière, 75013 Paris, France</mods:affiliation><country xml:lang="fr">France</country><wicri:regionArea>INSERM U.289, Hôpital de la Salpêtrière, 75013 Paris</wicri:regionArea></affiliation></author><author><name sortKey="Hirsch, E C" sort="Hirsch, E C" uniqKey="Hirsch E" first="E. C." last="Hirsch">E. C. Hirsch</name><affiliation wicri:level="1"><mods:affiliation>INSERM U.289, Hôpital de la Salpêtrière, 75013 Paris, France</mods:affiliation><country xml:lang="fr">France</country><wicri:regionArea>INSERM U.289, Hôpital de la Salpêtrière, 75013 Paris</wicri:regionArea></affiliation><affiliation wicri:level="1"><mods:affiliation> E. C. Hirsch, INSERM U.289, Hôpital de la Salpêtrière, 47 boulevard de l'Hôpital, 75651 Paris cedex 13, France</mods:affiliation><country xml:lang="fr">France</country><wicri:regionArea> E. C. Hirsch, INSERM U.289, Hôpital de la Salpêtrière, 47 boulevard de l'Hôpital, 75651 Paris cedex 13</wicri:regionArea></affiliation></author></analytic><monogr></monogr><series><title level="j">European Journal of Neuroscience</title><idno type="ISSN">0953-816X</idno><idno type="eISSN">1460-9568</idno><imprint><publisher>Blackwell Publishing Ltd</publisher><pubPlace>Oxford, UK</pubPlace><date type="published" when="1995-06">1995-06</date><biblScope unit="volume">7</biblScope><biblScope unit="issue">6</biblScope><biblScope unit="page" from="1199">1199</biblScope><biblScope unit="page" to="1209">1209</biblScope></imprint><idno type="ISSN">0953-816X</idno></series><idno type="istex">D289E5597D5F82D7859F046D67427D8151FBBFF5</idno><idno type="DOI">10.1111/j.1460-9568.1995.tb01110.x</idno><idno type="ArticleID">EJN1199</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0953-816X</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>GABAergic neurons</term><term>Parkinsonian syndrome</term><term>basal ganglia</term><term>in situ hybridization</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">The effects of nigrostriatal denervation and L‐dopa therapy on GABAergic neurons were analysed in patients with Parkinson's disease and in monkeys rendered parkinsonian by MPTP intoxication. The expression of the messenger RNA coding for the 67 kDa isoform of glutamic acid decarboxylase (GAD67 mRNA), studied by quantitative in situ hybridization, was used as an index of the GABAergic activity of the striatal neurons. A significant increase in GAD67 mRNA expression, generalized to all GABAergic neurons, was observed in MPTP‐treated monkeys compared to control monkeys in the putamen and caudate nucleus (+44 and +67% respectively), but not in the ventral striatum. L‐Dopa therapy significantly reduced GAD67 mRNA expression in the putamen and caudate nucleus to levels similar to those found in control monkeys. However, the return to normal of GAD67 mRNA expression was not homogeneous across all neurons since it was followed by an increase of labelling in one subpopulation of GABAergic neurons and a decrease in another. These data suggest that in MPTP‐treated monkeys the degeneration of nigrostriatal dopaminergic neurons results in a generalized increase in GABAergic activity in all the GABAergic neurons of the striatum, which is partially reversed by L‐dopa therapy. As the expression of GAD67 mRNA is less intense in the ventral than in the dorsal striatum, this increase in striatal GABAergic activity may be related to the severity of nigrostriatal denervation. In parkinsonian patients who had been chronically treated with L‐dopa, GAD67 mRNA expression was significantly decreased in all GABAergic neurons, in the caudate nucleus (by 44%), putamen (by 43.5%) and ventral striatum (by 26%). The opposite variation of GAD67 mRNA in patients with Parkinson's disease, compared with MPTP‐treated monkeys, might be explained by the combination of chronic nigrostriatal denervation and long‐term L‐dopa therapy.</div></front></TEI></record>Pour manipuler ce document sous Unix (Dilib)
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