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Aging enables Ca2+ overload and apoptosis induced by amyloid-β oligomers in rat hippocampal neurons: Neuroprotection by non-steroidal anti-inflammatory drugs and r-flurbiprofen in aging neurons

AutorCalvo-Rodríguez, María; García-Durillo, Mónica; Villalobos, Carlos ; Núñez, Lucía
Palabras claveHippocampal neurons
Calcium
R-flurbiprofen
Aging
Aβ42 oligomers
Mitochondria
Non-steroidal anti-inflammatory drugs
NSAIDs
Alzheimer’s disease
Fecha de publicación2016
EditorIOS Press
CitaciónJournal of Alzheimer's Disease 54(1): 207-221 (2016)
ResumenThe most important risk factor for Alzheimer's disease (AD) is aging. Neurotoxicity in AD has been linked to dyshomeostasis of intracellular Ca induced by small aggregates of the amyloid-β peptide 1- (Aβ oligomers). However, how aging influences susceptibility to neurotoxicity induced by Aβ 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 Ca dishomeostasis and neuron cell death induced by Aβ oligomers. In addition, we tested whether non-steroidal antiinflammatory drugs (NSAIDs) and R-flurbiprofen prevent apoptosis acting on subcellular Ca in aged neurons.We found that Aβ 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 Ca responses induced by Aβ oligomers increased dramatically with culture age. At low concentrations, NSAIDs and the enantiomer R-flurbiprofen lacking antiinflammatory activity prevent Ca overload and neuron cell death induced by Aβ oligomers in aged neurons. However, at high concentrations R-flurbiprofen induces apoptosis. Thus, Aβ oligomers promote Ca 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 Ca overload.
URIhttp://hdl.handle.net/10261/158071
DOI10.3233/JAD-151189
Identificadoresdoi: 10.3233/JAD-151189
e-issn: 1875-8908
issn: 1387-2877
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