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oai:uvadoc.uva.es:10324/218112021-06-23T09:52:15Zcom_10324_1134com_10324_931com_10324_894col_10324_1213

Calvo Rodríguez, María García Durillo, Mónica Villalobos Jorge, Carlos Núñez Llorente, Lucía 2016-12-16T12:26:56Z 2016-12-16T12:26:56Z 2016 J Alzheimers Dis. 2016 Jul 22;54(1):207-21 1387-2877 http://uvadoc.uva.es/handle/10324/21811 10.3233/JAD-151189 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. eng info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by-nc-nd/4.0/ Attribution-NonCommercial-NoDerivatives 4.0 International Alzheimer, Enfermedad de 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 info:eu-repo/semantics/article