Differential effects of aging on binding sites of the activated NMDA receptor complex in mice

The NMDA receptor site has been shown to be vulnerable to the effects of aging. Decreases in binding to the receptor site of up to 50% have been reported in aged animals. The present study was designed to quantitate and compare the effects of aging on multiple binding sites of the NMDA receptor complex in various brain regions. Autoradiography with 3H]glutamate, 3H]CPP, 3H]glycine, 3H]MK801 and 3H]TCP was performed on brain sections from 3, 10 and 28-30 month old C57B1/6 mice. The percent declines between 3 and 28-30 months of age in 3H]-glutamate (15-35% declines) and 3H]CPP (20-42% declines) binding were similar within most cortical regions and the caudate nucleus but 3H]glutamate binding showed less change (0-11% declines) than 3H]CPP (13-27% declines) in the occipital/temporal cortex and hippocampal regions. 3H]MK801 and 3H]TCP binding, stimulated by 10 microM glutamate, exhibited intermediate aging changes between the glycine and NMDA sites, both in percent decline (3-28% and 0-26%, respectively) and in the number of brain regions involved. 3H]Glycine binding, stimulated by 10 microM glutamate, showed no significant overall effect of age (declines ranged from 0-34%). 3H]CPP binding was significantly more affected than 3H]glycine binding in many regions. These results suggest that aging has heterogeneous effects on different sites on the NMDA receptor complex throughout the brain and on NMDA receptor agonist versus antagonist binding in selected brain regions.