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dc.contributor.authorYuste Jiménez, José Enrique
dc.contributor.authorEcheverry, M. B.
dc.contributor.authorRos Bernal, Francisco
dc.contributor.authorGómez, Aurora
dc.contributor.authorRos Gómez, Carmen María
dc.contributor.authorCampuzano Brando, Carmen María
dc.contributor.authorFernández Villalba, Emiliano
dc.contributor.authorHerrero Ezquerro, María Trinidad
dc.date.accessioned2013-07-03T10:45:18Z
dc.date.available2013-07-03T10:45:18Z
dc.date.issued2012
dc.identifier.citationYUSTE, J. E., et al. 7-Nitroindazole down-regulates dopamine/DARPP-32 Signaling in neostriatal neurons in a rat model of Parkinson’s Disease. Neuropharmacology, 2012.ca_CA
dc.identifier.issn0028-3908
dc.identifier.urihttp://hdl.handle.net/10234/69341
dc.description.abstractNeuronal nitric oxide synthase (nNOS) is involved in the regulation of diverse intracellular messenger systems in the brain. Nitric Oxide (NO) contributes to inducing signaling cascades that involve a complex pattern of phosphorylation of DARPP-32 (in Thr-34), which controls the phosphoproteins involved in neuronal activation. However, the role of NO in the pathophysiology of Parkinson's disease (PD) and its effect in striatal neurons have been scarcely explored. In the present work, we investigate the effects of a nitric oxide synthase (NOS) inhibitor, 7-nitroindazole (7-NI) in the nigrostriatal pathway of striatal 6-hydroxydopamine (6-OHDA) lesioned rats. Our quantitative histological findings show that treatment with 7-NI significantly reduced 6-OHDA-induced dopaminergic damage in the dorsolateral striatum and Substantia Nigra pars compacta (SNpc). Moreover, 6-OHDA lesioned rats show a significant increase of nNOS+ and Phospho-Thr34-DARPP-32+ cells, accompanied by a consequent decrease of total DARPP-32+ cells, which suggests an imbalance of NO activity in the DA-depleted striatum, which is also reflected in behavioral studies. Importantly, these effects are reverted in the group treated with 7-NI. These results show a clear link between the state of phosphorylation of DARPP-32 and parkinsonism, which is regulated by nNOS. This new evidence suggests a prominent role for nitric oxide in the neurotransmitter balance within the basal ganglia in the pathophysiology of experimental parkinsonism.ca_CA
dc.description.sponsorShipThis work was supported by grants from the Spanish Ministry of Science (SAF 2007-62262), FIS (PI/2010/02827) and CIBERNED (Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas).ca_CA
dc.format.extent10 p.ca_CA
dc.format.mimetypeapplication/pdfca_CA
dc.language.isoengca_CA
dc.publisherElsevierca_CA
dc.relation.isPartOfNeuropharmacology (2012) 63 (7)ca_CA
dc.rightsCopyright © 2012 Elsevier Ltd. All rights reservedca_CA
dc.rights.urihttp://rightsstatements.org/vocab/InC/1.0/*
dc.subject6-OHDAca_CA
dc.subjectDorsolateralca_CA
dc.subjectNeostriatumca_CA
dc.subjectSNpcca_CA
dc.subjectTHca_CA
dc.subjectnNOSca_CA
dc.subjectDARPP-32ca_CA
dc.subject7-NIca_CA
dc.subjectEBSTca_CA
dc.title7-Nitroindazole down-regulates dopamine/DARPP-32 signaling in neostriatal neurons in a rat model of Parkinson's diseaseca_CA
dc.typeinfo:eu-repo/semantics/articleca_CA
dc.identifier.doihttp://dx.doi.org/10.1016/j.neuropharm.2012.07.031
dc.rights.accessRightsinfo:eu-repo/semantics/openAccessca_CA
dc.relation.publisherVersionhttp://www.sciencedirect.com/science/article/pii/S002839081200367Xca_CA
dc.type.versioninfo:eu-repo/semantics/acceptedVersion


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