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Dadun > Depósito Académico > Facultad de Medicina > Departamento de Anatomía > DA - Medicina - Anatomía - Artículos de revista >

Sildenafil restores cognitive function without affecting β-amyloid burden in a mouse model of Alzheimer's disease
Autor(es) : Garcia-Osta, A. (Ana)
Aguirre, N. (Norberto)
Franco, R. (Rafael)
Garcia-Barroso, C. (Carolina)
Perez-Roldan, J.M. (J.M.)
Puerta, E. (Elena)
Ricobaraza, A. (Ana)
Hervias, I. (Isabel)
Cuadrado-Tejedor, M. (Mar)
Palabras clave : BDNF
CDK5
GSK3β
sildenafil
p-tau
Alzheimer's disease
Fecha incorporación: dic-2011
Editorial : Wiley-Blackwell
Versión del editor: http://doi.org/10.1111/j.1476-5381.2011.01517.x
ISSN: 0007-1188
Cita: Cuadrado-Tejedor M, Hervias I, Ricobaraza A, Puerta E, Perez-Roldan JM, Garcia-Barroso C, et al. Sildenafil restores cognitive function without affecting beta-amyloid burden in a mouse model of Alzheimer's disease. Br J Pharmacol 2011 Dec;164(8):2029-2041.
Resumen
Abstract BACKGROUND AND PURPOSE: Inhibitors of phosphodiesterase 5 (PDE5) affect signalling pathways by elevating cGMP, which is a second messenger involved in processes of neuroplasticity. In the present study, the effects of the PDE5 inhibitor, sildenafil, on the pathological features of Alzheimer's disease and on memory-related behaviour were investigated. EXPERIMENTAL APPROACH: Sildenafil was administered to the Tg2576 transgenic mouse model of Alzheimer's disease and to age-matched negative littermates (controls). Memory function was analysed using the Morris water maze test and fear conditioning tasks. Biochemical analyses were performed in brain lysates from animals treated with saline or with sildenafil. KEY RESULTS: Treatment of aged Tg2576 animals with sildenafil completely reversed their cognitive impairment. Such changes were accompanied in the hippocampus by a reduction of tau hyperphosphorylation and a decrease in the activity of glycogen synthase kinase 3β (GSK3β) and of cyclin-dependent kinase 5 (CDK5) (p25/p35 ratio). Moreover, sildenafil also increased levels of brain-derived neurotrophic factor (BDNF) and the activity-regulated cytoskeletal-associated protein (Arc) in the hippocampus without any detectable modification of brain amyloid burden. CONCLUSIONS AND IMPLICATIONS: Sildenafil improved cognitive functions in Tg2576 mice and the effect was not related to changes in the amyloid burden. These data further strengthen the potential of sildenafil as a therapeutic agent for Alzheimer's disease.
Enlace permanente: http://hdl.handle.net/10171/22826
Aparece en las colecciones: DA - Farmacia - Farmacología - Artículos de revista
DA - CIMA - Neurociencias - Neurofarmacología y conducta - Artículos de Revista
DA - Medicina - Anatomía - Artículos de revista

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Fichero:  bph2011Aguirre.pdf
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