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The PDE7 inhibitor S14 induces neurogenesis in vitro and in a rodent model of Parkinson disease

AuthorsMorales-García, José A. ; Pérez Castillo, Ana ; Redondo, Miriam ; Alonso-Gil, Sandra ; Santos, Ángel; Martínez, Ana
Issue Date2013
PublisherKenes International
CitationAP/PD 2013
Abstract[Introduction]: Different studies have suggested that cyclic AMP (cAMP) levels play an important role in neurodegenerative disorders, such as Parkinson Disease (PD). Phosphodiesterase 7 (PDE7), a specific cAMP phosphodiesterase, is very abundant in the brain; however its precise role in this tissue is almost unknown. We have recently shown that a specific inhibitor of PDE7, named S14, prevents dopaminergic cell death in cellular and rodent models of PD (Morales-Garcia et al. PLoS One 2011, 6:e17240). [Objectives]: Analysis in vitro and in vivo of the role of S14 on neurogenesis in basal conditions and in a rodent model of PD (injection of lipopolysaccharide (LPS) into the substantia nigra pars compacta (SNpc). [Methods]: Cultures of neurospheres were established from the subgranular zone of adult rats or from ventral mesencephalon of rat embryos and some of the cultures were incubated with S14. Control adult rats and rats injected with LPS were treated with the S14 compound and neurogenesis in different parts of the brain was evaluated. [Results]: Treatment of neurospheres with S14 elicited an increase in the number of these neurospheres and a differentiation toward a dopaminergic phenotype. Control rats and LPS-lesioned animals presented an increase in the number of proliferating progenitor cells and in the number of new neurons (including dopaminergic cells) in the subventricular zone, subgranular zone of the dentate gyrus of the hippocampus, and in the SNpc. Conclusions: These results show that PDE7 inhibitors, and specifically S14, may hold promise for the treatment of neurodegenerative disorders particularly PD
DescriptionResumen del póster presentado a la "11th International Conference on Alzheimer's & Parkinson's Diseases" celebrada del 6 al 10 de marzo de 2013 en Florencia (Italia).
Appears in Collections:(IQM) Comunicaciones congresos
(IIBM) Comunicaciones congresos
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