Y. Nagata et al., D-SERINE CONTENT AND D-[H-3]SERINE BINDING IN THE BRAIN-REGIONS OF THE SENESCENCE-ACCELERATED MOUSE, Mechanism of ageing and development, 104(2), 1998, pp. 115-124
An established senescence-accelerated model mouse strain, SAMP8, shows
the deterioration of learning and memory compared with a normal contr
ol strain, SAMR1. D-Serine binds to strychnine-insensitive glycine bin
ding sites of the N-methyl-D-aspartate (NMDA) receptor complex, and en
hances glutamate binding to the receptor complex. To investigate the r
elationship of endogenous brain D-serine and the brain dysfunction cau
sed by aging, the level of brain free D-serine and the D-[H-3]serine b
inding to the brain samples were examined using the SAMP8 and SAMR1 mi
ce. The free D-serine level was highest in the cerebral frontal and oc
cipital cortices in both the SAMP8 and SAMR1; no difference in the D-s
erine level was shown between the two strains. A receptor autoradiogra
phical analysis showed that the D-[H-3]serine binding to the brain sec
tion was highest in the hippocampus, and the binding in the SAMP8 brai
ns was lower than that of the SAMR1. The D-[H-3]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 va
lue of the dissociation constant K-d for the SAMP8 was similar to that
of the SAMR1. These results suggest that the number of D-[H-3]serine
binding sites was decreased in the SAMP8 compared to the SAMR1, but th
e affinity of D-[H-3]serine to the binding sites was not altered. Thes
e results support the view that a decrease of NMDA receptor complex is
involved in the age-related neural dysfunction of SAMP8 mice. (C) 199
8 Elsevier Science Ireland Ltd. All rights reserved.