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Título: Aging Enables Ca2+ Overload and Apoptosis Induced by Amyloid- Oligomers in Rat Hippocampal Neurons: Neuroprotection by Non-Steroidal Anti-Inflammatory Drugs and R-Flurbiprofen in Aging Neurons
Autor: Calvo Rodríguez, María
García Durillo, Mónica
Villalobos, Carlos
Nuñez Llorente, Lucía
Año del Documento: 2016
Editorial: IOS Press
Descripción: Producción Científica
Documento Fuente: J Alzheimers Dis. 2016 Jul 22;54(1):207-21
Resumen: The most important risk factor for Alzheimer’s disease (AD) is aging. Neurotoxicity in AD has been linked to dyshomeostasis of intracellular Ca2+ induced by small aggregates of the amyloid- peptide 1-42 (A 42 oligomers). However, how aging influences susceptibility to neurotoxicity induced by A 42 oligomers is unknown. In this study, we used longterm cultures of rat hippocampal neurons, a model of neuronal in vitro aging, to investigate the contribution of aging to Ca2+ dishomeostasis and neuron cell death induced by A 42 oligomers. In addition, we tested whether non-steroidal antiinflammatory drugs (NSAIDs) and R-flurbiprofen prevent apoptosis acting on subcellular Ca2+ in aged neurons.We found that A 42 oligomers have no effect on young hippocampal neurons cultured for 2 days in vitro (2 DIV). However, they promoted apoptosis modestly in mature neurons (8 DIV) and these effects increased dramatically after 13 DIV, when neurons display many hallmarks of in vivo aging. Consistently, cytosolic and mitochondrial Ca2+ responses induced by A 42 oligomers increased dramatically with culture age. At low concentrations, NSAIDs and the enantiomer R-flurbiprofen lacking antiinflammatory activity prevent Ca2+ overload and neuron cell death induced by A 42 oligomers in aged neurons. However, at high concentrations R-flurbiprofen induces apoptosis. Thus, A 42 oligomers promote Ca2+ overload and neuron cell death only in aged rat hippocampal neurons. These effects are prevented by low concentrations of NSAIDs and R-flurbiprofen acting on mitochondrial Ca2+ overload.
Materias (normalizadas): Alzheimer
ISSN: 1387-2877
Revisión por Pares: SI
DOI: 10.3233/JAD-151189
Patrocinador: Ministerio de Economía y Competitividad (BFU2012- 627 37146)
Junta de Castilla y León (VA145U13, 625 BIO/VA33/13, BIO103/VA45/11)
Version del Editor: http://www.iospress.nl/journal/journal-of-alzheimers-disease/
Idioma: eng
URI: http://uvadoc.uva.es/handle/10324/21811
Derechos: info:eu-repo/semantics/openAccess
Aparece en las colecciones:DEP06 - Artículos de revista

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