dc.contributor.author | Aristieta Arbelaiz, Asier | |
dc.contributor.author | Azkona Mendoza, Garikoitz | |
dc.contributor.author | Sagarduy Crespo, Ainhoa | |
dc.contributor.author | Miguélez Palomo, Cristina | |
dc.contributor.author | Ruiz Ortega, José Ángel | |
dc.contributor.author | Sánchez Pernaute, Rosario | |
dc.contributor.author | Ugedo Urruela, Luisa | |
dc.date.accessioned | 2013-01-11T19:04:00Z | |
dc.date.available | 2013-01-11T19:04:00Z | |
dc.date.issued | 2012-08-06 | |
dc.identifier.citation | PLoS ONE 7(8) : (2012) // e42652 | es |
dc.identifier.issn | 1932-6203 | |
dc.identifier.uri | http://hdl.handle.net/10810/9211 | |
dc.description | 14 p. | es |
dc.description.abstract | L-DOPA is the most effective treatment for Parkinson's disease (PD), but prolonged use leads to disabling motor complications including dyskinesia. Strong evidence supports a role of the subthalamic nucleus (STN) in the pathophysiology of PD whereas its role in dyskinesia is a matter of controversy. Here, we investigated the involvement of STN in dyskinesia, using single-unit extracellular recording, behavioural and molecular approaches in hemi-parkinsonian rats rendered dyskinetic by chronic L-DOPA administration. Our results show that chronic L-DOPA treatment does not modify the abnormal STN activity induced by the 6-hydroxydopamine lesion of the nigrostriatal pathway in this model. Likewise, we observed a loss of STN responsiveness to a single L-DOPA dose both in lesioned and sham animals that received daily L-DOPA treatment. We did not find any correlation between the abnormal involuntary movement (AIM) scores and the electrophysiological parameters of STN neurons recorded 24 h or 20–120 min after the last L-DOPA injection, except for the axial subscores. Nonetheless, unilateral chemical ablation of the STN with ibotenic acid resulted in a reduction in global AIM scores and peak-severity of dyskinesia. In addition, STN lesion decreased the anti-dyskinetogenic effect of buspirone in a reciprocal manner. Striatal protein expression was altered in dyskinetic animals with increases in ΔFosB, phosphoDARPP-32, dopamine receptor (DR) D3 and DRD2/DRD1 ratio. The STN lesion attenuated the striatal molecular changes and normalized the DRD2/DRD1 ratio. Taken together, our results show that the STN plays a role, if modest, in the physiopathology of dyskinesias. | es |
dc.description.sponsorship | This study was supported by grants from the Spanish Ministry of Science SAF 2009-08664 (LU), the department of Industry of the Basque Government S-PE10UN24 (LU and RSP) and Kutxa Obra social (RSP). AA and AS have a fellowship from the University of the Basque Country. The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of manuscript. | es |
dc.language.iso | eng | es |
dc.publisher | Public Library of Science | es |
dc.rights | info:eu-repo/semantics/openAccess | es |
dc.subject | deep brain-stimulation | es |
dc.subject | abnormal involuntary movements | es |
dc.subject | Parkinsons-disease | es |
dc.subject | high-frequency stimulation | es |
dc.subject | dyskinesia | es |
dc.subject | neuronal-activity | es |
dc.subject | basal ganglia | es |
dc.subject | receptor antagonist | es |
dc.subject | substantia-nigra | es |
dc.subject | globus-pallidus | es |
dc.title | The Role of the Subthalamic Nucleus in L-DOPA Induced Dyskinesia in 6-Hydroxydopamine Lesioned Rats | es |
dc.type | info:eu-repo/semantics/article | es |
dc.rights.holder | © Aristieta et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. | es |
dc.relation.publisherversion | http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0042652 | es |
dc.identifier.doi | 10.1371/journal.pone.0042652 | |
dc.departamentoes | Farmacología | es_ES |
dc.departamentoeu | Farmakologia | es_ES |
dc.subject.categoria | AGRICULTURAL AND BIOLOGICAL SCIENCES | |
dc.subject.categoria | MEDICINE | |
dc.subject.categoria | BIOCHEMISTRY AND MOLECULAR BIOLOGY | |