7-Nitroindazole down-regulates dopamine/DARPP-32 signaling in neostriatal neurons in a rat model of Parkinson's disease
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Otros documentos de la autoría: Yuste Jiménez, José Enrique; Echeverry, M. B.; Ros Bernal, Francisco; Gómez, Aurora; Ros Gómez, Carmen María; Campuzano Brando, Carmen María; Fernández Villalba, Emiliano; Herrero Ezquerro, María Trinidad
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Título
7-Nitroindazole down-regulates dopamine/DARPP-32 signaling in neostriatal neurons in a rat model of Parkinson's diseaseAutoría
Fecha de publicación
2012Editor
ElsevierISSN
0028-3908Cita bibliográfica
YUSTE, 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.Tipo de documento
info:eu-repo/semantics/articleVersión de la editorial
http://www.sciencedirect.com/science/article/pii/S002839081200367XVersión
info:eu-repo/semantics/acceptedVersionPalabras clave / Materias
Resumen
Neuronal 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 ... [+]
Neuronal 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. [-]
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Neuropharmacology (2012) 63 (7)Derechos de acceso
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