Alteration of CREB phosphorylation and spatial memory deficits in aged 129T2/Sv mice

Phosphorylation of cAMP-response element binding protein (CREB) is required for hippocampus-dependent long-term memory formation. The present study was designed to determine whether spatial memory deficits in aged mice were associated with alteration of hippocampal CREB phosphoryl Lit ion. We examined the temporal pattern of CREB activation in 5-6 and 23-24-month-old 129T2/Sv mice trained oil a spatial reference memory task in the water maze. Phosphorylated CREB (I)CREB), total CREB (I-CREB) and c-Fos immunoreactivity (ir) were measured at four time points after the end of training. In young mice, pCREB-ir was significantly increased 15 and 60 min after training in the CA I region and dentate gyrus. In aged mice sacrificed 15 min after training, pCREB-ir ill these Structures was reduced whereas t-CREB-ir remained unchanged compared to respective young-adults. An age-related reduction of c-Fos-ir also occurred selectively in hippocampal CAI region. Since reduced pCREB-ir in CAI from the 15 min-aged group Strongly correlated with individual learning performance, we suggest that altered CREB phosphorylation in CAI may account for spatial memory impairments during normal aging. (C) 2007 Elsevier Inc. All rights reserved.