The aging of the NMDA receptor complex.

N-methyl-D-aspartate (NMDA) receptors are present at high density in the cerebral cortex and hippocampus and play an important role in learning and memory. These receptors are negatively affected by the aging process, but this effect does not appear to be uniform throughout the cortex and hippocampus. This review discusses the age-associated changes that occur in the different binding sites of the NMDA receptor complex, in the expression of subunits that comprise the complex, in the electrophysiological properties of the receptor, and in the ability of NMDA to stimulate the release of other transmitters. Spatial memory and some types of passive avoidance memory tasks have been shown to involve NMDA receptors. Aged animals show deficiencies in the performance of these tasks, as compared to young, and some studies have identified an association between lower densities of NMDA receptor binding and poor memory performance. A number of drug and diet interventions have shown potential for reversing or slowing the effects of aging on the NMDA receptor. These studies suggest that the development of treatments that are aimed at preventing or reversing the effects of aging on the NMDA receptor will aid in preventing the memory declines that are associated with aging.