D-Serine content and D-[³H]serine binding in the brain regions of the senescence-accelerated mouse

An established senescence-accelerated model mouse strain, SAMP8, shows the deterioration of learning and memory compared with a normal control strain, SAMR1. D-Serine binds to strychnine-insensitive glycine binding sites of the N-methyl-D-aspartate (NMDA) receptor complex, and enhances glutamate binding to the receptor complex. To investigate the relationship of endogenous brain D-serine and the brain dysfunction caused by aging, the level of brain free D-serine and the D-[³H]serine binding to the brain samples were examined using the SAMP8 and SAMR1 mice. The free D-serine level was highest in the cerebral frontal and occipital cortices in both the SAMP8 and SAMR1; no difference in the D-serine level was shown between the two strains. A receptor autoradiographical analysis showed that the D-[³H]serine binding to the brain section was highest in the hippocampus, and the binding in the SAMP8 brains was lower than that of the SAMR1. The D-[³H]serine binding to the crude cerebral membranes indicated that the value of the total binding sites for the SAMP8 was lower than that for the SAMR1, whereas the value of the dissociation constant K(d) for the SAMP8 was similar to that of the SAMR1. These results suggest that the number of D-[³H]serine binding sites was decreased in the SAMP8 compared to the SAMR1, but the affinity of D-[³H]serine to the binding sites was not altered. These results support the view that a decrease of NMDA receptor complex is involved in the age-related neural dysfunction of SAMP8 mice.