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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.
Quintana A., Sgambato-Faure V., Savasta M.
Neurobiology of Disease 48, 3 (2012) 379-90 - http://www.hal.inserm.fr/inserm-00742517
Effects of L-DOPA and STN-HFS dyskinesiogenic treatments on NR2B regulation in basal ganglia in the rat model of Parkinson's disease.
Adrien Quintana1, Véronique Sgambato-Faure () 1, Marc Savasta () 1
1 :  GIN - U836 - Grenoble Institut des Neurosciences
INSERM : U836 – Université Joseph Fourier - Grenoble I – CHU Grenoble – CEA : DSV/IRTSV
UJF - Site Santé La Tronche - BP 170 - 38042 Grenoble Cedex 9
INSERM U836, équipe 10, Dynamique des réseaux neuronaux du mouvement
NR2B hyperphosphorylation driven by L-DOPA and STN-HFS
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.
Sciences du Vivant/Neurosciences
Sciences du Vivant/Médecine humaine et pathologie/Physiologie

Articles dans des revues avec comité de lecture
Neurobiology of Disease (Neurobiol Dis)
Publisher Elsevier
ISSN 0969-9961 (eISSN : 1095-953X)

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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