RT info:eu-repo/semantics/article
T1 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
A1 Calvo Rodríguez, María
A1 García Durillo, Mónica
A1 Villalobos Jorge, Carlos
A1 Núñez Llorente, Lucía
K1 Alzheimer, Enfermedad de
AB The most important risk factor for Alzheimer’s disease (AD) is aging. Neurotoxicity in AD has been linked todyshomeostasis 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 longtermcultures of rat hippocampal neurons, a model of neuronal in vitro aging, to investigate the contribution of aging toCa2+ dishomeostasis and neuron cell death induced by A 42 oligomers. In addition, we tested whether non-steroidal antiinflammatorydrugs (NSAIDs) and R-flurbiprofen prevent apoptosis acting on subcellular Ca2+ in aged neurons.We found thatA 42 oligomers have no effect on young hippocampal neurons cultured for 2 days in vitro (2 DIV). However, they promotedapoptosis modestly in mature neurons (8 DIV) and these effects increased dramatically after 13 DIV, when neurons displaymany hallmarks of in vivo aging. Consistently, cytosolic and mitochondrial Ca2+ responses induced by A 42 oligomersincreased dramatically with culture age. At low concentrations, NSAIDs and the enantiomer R-flurbiprofen lacking antiinflammatoryactivity prevent Ca2+ overload and neuron cell death induced by A 42 oligomers in aged neurons. However, athigh concentrations R-flurbiprofen induces apoptosis. Thus, A 42 oligomers promote Ca2+ overload and neuron cell deathonly in aged rat hippocampal neurons. These effects are prevented by low concentrations of NSAIDs and R-flurbiprofenacting on mitochondrial Ca2+ overload.
PB IOS Press
SN 1387-2877
YR 2016
FD 2016
LK http://uvadoc.uva.es/handle/10324/21811
UL http://uvadoc.uva.es/handle/10324/21811
LA eng
NO J Alzheimers Dis. 2016 Jul 22;54(1):207-21
NO Producción Científica
DS UVaDOC
RD 22-nov-2024