UNASSIGNED: @entity75 after insult and @entity73 are related to excitotoxicity and strongly influenced by aging, yet mechanisms of aging-dependent susceptibility to excitotoxicity are poorly known. Several non-steroidal anti-inflammatory drugs (NSAIDs) may prevent excitotoxicity and @entity73 in the elderly by an unknown mechanism. Interestingly, after several weeks in vitro, hippocampal neurons display important hallmarks of neuronal aging in vivo. Accordingly, @entity35 hippocampal neurons cultured for several weeks were used to investigate mechanisms of aging-related susceptibility to excitotoxicity and neuroprotection by NSAIDs. We found that @entity143 increased cytosolic @entity141 concentration in young, mature and aged neurons but only promoted apoptosis in aged neurons. Resting @entity141 levels and responses to @entity143 increased with time in culture which correlated with changes in expression of @entity143 receptor subunits. In addition, @entity143 promoted mitochondrial @entity141 uptake only in aged cultures. Consistently, specific inhibition of mitochondrial @entity141 uptake decreased apoptosis. Finally, we found that a series of NSAIDs depolarized mitochondria and inhibited mitochondrial @entity141 overload, thus preventing @entity143 -induced apoptosis in aged cultures. We conclude that mitochondrial @entity141 uptake is critical for age-related susceptibility to excitotoxicity and neuroprotection by NSAIDs. @entity35 hippocampal neurons aged in culture were used to investigate mechanisms of age-related susceptibility to excitotoxicity and neuroprotection by non-steroidal anti-inflammatory drugs (NSAIDs). Old neurons display enhanced resting @entity460 and responses to @entity143 along with increased expression of @entity143 receptor subunits @entity4474 and @entity4476 altogether favoring mitochondrial @entity460 overload. NSAIDs protect neurons against excitotoxicity acting on mitochondrial @entity460 uptake. @entity143 , @entity1024 .

Susceptibility to excitotoxicity in aged hippocampal cultures and neuroprotection by non-steroidal anti-inflammatory drugs: role of mitochondrial XXXX .

@entity1024 :: ('CHEBI:31882', 'Chemical') :: ['N methyl d-aspartate'] @entity35 :: ('10116', 'Species') :: ['rat', 'Rat'] @entity75 :: ('MESH:D001927', 'Disease') :: ['Brain damage'] @entity73 :: ('MESH:D003072', 'Disease') :: ['cognitive decline'] @entity4476 :: ('24409(Tax:10116)', 'Gene') :: ['NR2A'] @entity4474 :: ('24408(Tax:10116)', 'Gene') :: ['NR1'] @entity143 :: ('CHEBI:6121', 'Chemical') :: ['NMDA'] @entity460 :: ('MESH:D002118', 'Chemical') :: ['calcium'] @entity141 :: ('CHEBI:29108', 'Chemical') :: ['Ca(2+)']
@entity460 :: (MESH:D002118,Chemical) :: ['calcium']
