Different age-related changes in NMDA and glycine receptors in the rat brain.

We investigated the age-related changes of N-methyl-d-aspartate (NMDA) and strychnine-insensitive glycine receptors in the brain from Fischer rats aged 3 weeks (immature), 6 months (adult), 12 months (mature), 18 months (middle-aged) and 24 months (aged) using receptor autoradiography. [(3)H]MK-801 and [(3)H]glycine were used to label the NMDA receptor and the glycine receptor, respectively. In immature rats, [(3)H]MK-801 binding showed a significant decline only in the nucleus accumbens, whereas [(3)H]glycine binding exhibited a significant increase in the frontal cortex, parietal cortex, striatum and thalamus as compared with young rats. In mature, middle-aged and aged rats, [(3)H]MK-801 binding showed no significant change in the brain. In contrast, [(3)H]glycine binding showed a conspicuous reduction in the striatum and hippocampal CA3 sector and thalamus from mature rats. Thereafter, the age-related reduction in [(3)H]glycine binding was observed in all brain areas of middle-aged and aged rats. These results demonstrate that the glycine receptor in the rat brain is far more susceptible to aging processes than the NMDA receptor. Furthermore, they suggest the conspicuous differences in the developmental pattern between NMDA and glycine receptors in the rat brain after birth. These findings suggest that glycine receptor in the brain is primarily and severely affected in aging processes and this may lead to age-related neurological deficits.