PMID: identifiant
de la référence Pubmed : |
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 (22759925) |
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| titre : |
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Effects of L-DOPA and STN-HFS dyskinesiogenic treatments on NR2B regulation in basal ganglia in the rat model of Parkinson's disease. |
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| auteur(s) : |
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Adrien Quintana1, Véronique Sgambato-Faure ( ) 1, Marc Savasta () 1 |
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| laboratoire : |
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| Équipe de recherche : |
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INSERM U836, équipe 10, Dynamique des réseaux neuronaux du mouvement |
| titre abrégé : |
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NR2B hyperphosphorylation driven by L-DOPA and STN-HFS |
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| résumé : |
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Dyskinesia is a major side effect of chronic levodopa (L-DOPA) administration, the reference treatment for Parkinson's disease (PD). High-frequency stimulation of the subthalamic nucleus (STN-HFS) alleviates parkinsonian motor symptoms and indirectly improves dyskinesia by decreasing L-DOPA requirement. However, inadequate stimulation can also trigger dyskinetic movements in PD patients and animal models. Here, we investigated the possible association between L-DOPA- and STN-HFS-induced dyskinesia and regulation of the NR2B subunit of NMDA receptors in the rodent model of PD. We subjected 6-OHDA-lesioned rats to HFS for 1h, at an intensity triggering forelimb dyskinesia. Other 6-OHDA-lesioned rats were treated with chronic high doses of L-DOPA for ten days, to induce abnormal involuntary movements. The 6-OHDA lesion regulated NR2B only in the SNr, where the activation of NR2B was observed (as assessed by phosphorylation of the Tyr(1472) residue). Both STN-HFS and L-DOPA dyskinesiogenic treatments induced NR2B activation in the STN and EP, but only L-DOPA triggered NR2B hyperphosphorylation in the striatum. Finally, the use of CP-101,606 exacerbated L-DOPA-induced motor behavior and associated NR2B hyperphosphorylation in the striatum, STN and EP. Thus, NR2B activation in basal ganglia structures is correlated with dyskinesia. |
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| domaine : |
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langue du texte
intégral : |
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Anglais |
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| ISSN : |
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0969-9961 |
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| type de publication : |
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Articles dans des revues avec comité de lecture |
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| DOI : |
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10.1016/j.nbd.2012.06.009 |
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| journal : |
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| Neurobiology of Disease (Neurobiol Dis) |
| Publisher |
Elsevier |
| ISSN |
0969-9961 (eISSN : 1095-953X) |
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| Audience : |
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internationale |
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| date de publication : |
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12/2012 |
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date de publication
électronique : |
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30/06/2012 |
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| volume : |
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48 |
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| numéro : |
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3 |
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| page, identifiant, ... : |
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379-90 |
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| contrat, financement : |
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Institut National de la Santé et de la Recherche Médicale; le Ministère de la Recherche et des Nouvelles Technologies; Région Rhône-Alpes (Cluster no.11); Association France Parkinson; Fondation NRJ-Institut de France. |
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| Projet ANR : |
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| Référence du projet |
ANR-05-NEUR-013-01 |
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