Distinct Changes in cAMP and Extracellular Signal-Regulated Protein Kinase Signalling in L-DOPA-Induced Dyskinesia
Identifieur interne : 001A48 ( Main/Exploration ); précédent : 001A47; suivant : 001A49Distinct Changes in cAMP and Extracellular Signal-Regulated Protein Kinase Signalling in L-DOPA-Induced Dyskinesia
Auteurs : Emanuela Santini [Suède] ; Veronique Sgambato-Faure [France] ; Qin Li [France, République populaire de Chine] ; Marc Savasta [France] ; Sandra Dovero [France] ; Gilberto Fisone [Suède] ; Erwan Bezard [France, République populaire de Chine]Source :
- PLoS ONE [ 1932-6203 ] ; 2010.
Abstract
In rodents, the development of dyskinesia produced by L-DOPA in the dopamine-depleted striatum occurs in response to increased dopamine D1 receptor-mediated activation of the cAMP - protein kinase A and of the Ras-extracellular signal-regulated kinase (ERK) signalling pathways. However, very little is known, in non-human primates, about the regulation of these signalling cascades and their association with the induction, manifestation and/or maintenance of dyskinesia.
We here studied, in the gold-standard non-human primate model of Parkinson's disease, the changes in PKA-dependent phosphorylation of DARPP-32 and GluR1 AMPA receptor, as well as in ERK and ribosomal protein S6 (S6) phosphorylation, associated to acute and chronic administration of L-DOPA. Increased phosphorylation of DARPP-32 and GluR1 was observed in both L-DOPA first-ever exposed and chronically-treated dyskinetic parkinsonian monkeys. In contrast, phosphorylation of ERK and S6 was enhanced preferentially after acute L-DOPA administration and decreased during the course of chronic treatment.
Dysregulation of cAMP signalling is maintained during the course of chronic L-DOPA administration, while abnormal ERK signalling peaks during the initial phase of L-DOPA treatment and decreases following prolonged exposure. While cAMP signalling enhancement is associated with dyskinesia, abnormal ERK signalling is associated with priming.
Url:
DOI: 10.1371/journal.pone.0012322
PubMed: 20808799
PubMed Central: 2925943
Affiliations:
- France, République populaire de Chine, Suède
- Aquitaine, Auvergne-Rhône-Alpes, Nouvelle-Aquitaine, Rhône-Alpes, Svealand
- Bordeaux, Grenoble, Pékin, Stockholm
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Le document en format XML
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<front><div type="abstract" xml:lang="en"><sec><title>Background</title>
<p>In rodents, the development of dyskinesia produced by L-DOPA in the dopamine-depleted striatum occurs in response to increased dopamine D1 receptor-mediated activation of the cAMP - protein kinase A and of the Ras-extracellular signal-regulated kinase (ERK) signalling pathways. However, very little is known, in non-human primates, about the regulation of these signalling cascades and their association with the induction, manifestation and/or maintenance of dyskinesia.</p>
</sec>
<sec><title>Methodology/Results</title>
<p>We here studied, in the gold-standard non-human primate model of Parkinson's disease, the changes in PKA-dependent phosphorylation of DARPP-32 and GluR1 AMPA receptor, as well as in ERK and ribosomal protein S6 (S6) phosphorylation, associated to acute and chronic administration of L-DOPA. Increased phosphorylation of DARPP-32 and GluR1 was observed in both L-DOPA first-ever exposed and chronically-treated dyskinetic parkinsonian monkeys. In contrast, phosphorylation of ERK and S6 was enhanced preferentially after acute L-DOPA administration and decreased during the course of chronic treatment.</p>
</sec>
<sec><title>Conclusion</title>
<p>Dysregulation of cAMP signalling is maintained during the course of chronic L-DOPA administration, while abnormal ERK signalling peaks during the initial phase of L-DOPA treatment and decreases following prolonged exposure. While cAMP signalling enhancement is associated with dyskinesia, abnormal ERK signalling is associated with priming.</p>
</sec>
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</analytic>
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</TEI>
<affiliations><list><country><li>France</li>
<li>République populaire de Chine</li>
<li>Suède</li>
</country>
<region><li>Aquitaine</li>
<li>Auvergne-Rhône-Alpes</li>
<li>Nouvelle-Aquitaine</li>
<li>Rhône-Alpes</li>
<li>Svealand</li>
</region>
<settlement><li>Bordeaux</li>
<li>Grenoble</li>
<li>Pékin</li>
<li>Stockholm</li>
</settlement>
</list>
<tree><country name="Suède"><region name="Svealand"><name sortKey="Santini, Emanuela" sort="Santini, Emanuela" uniqKey="Santini E" first="Emanuela" last="Santini">Emanuela Santini</name>
</region>
<name sortKey="Fisone, Gilberto" sort="Fisone, Gilberto" uniqKey="Fisone G" first="Gilberto" last="Fisone">Gilberto Fisone</name>
</country>
<country name="France"><region name="Auvergne-Rhône-Alpes"><name sortKey="Sgambato Faure, Veronique" sort="Sgambato Faure, Veronique" uniqKey="Sgambato Faure V" first="Veronique" last="Sgambato-Faure">Veronique Sgambato-Faure</name>
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<name sortKey="Bezard, Erwan" sort="Bezard, Erwan" uniqKey="Bezard E" first="Erwan" last="Bezard">Erwan Bezard</name>
<name sortKey="Dovero, Sandra" sort="Dovero, Sandra" uniqKey="Dovero S" first="Sandra" last="Dovero">Sandra Dovero</name>
<name sortKey="Li, Qin" sort="Li, Qin" uniqKey="Li Q" first="Qin" last="Li">Qin Li</name>
<name sortKey="Savasta, Marc" sort="Savasta, Marc" uniqKey="Savasta M" first="Marc" last="Savasta">Marc Savasta</name>
<name sortKey="Sgambato Faure, Veronique" sort="Sgambato Faure, Veronique" uniqKey="Sgambato Faure V" first="Veronique" last="Sgambato-Faure">Veronique Sgambato-Faure</name>
</country>
<country name="République populaire de Chine"><noRegion><name sortKey="Li, Qin" sort="Li, Qin" uniqKey="Li Q" first="Qin" last="Li">Qin Li</name>
</noRegion>
<name sortKey="Bezard, Erwan" sort="Bezard, Erwan" uniqKey="Bezard E" first="Erwan" last="Bezard">Erwan Bezard</name>
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</record>
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