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Recently, a substantial amount of free D-serine has been demonstrated in rat brain, although it has long been presumed that D-amino acids are uncommon in mammals. The anatomical distribution and age-related changes in endogenous D-serine have been examined here to obtain insight into its physiological functions. Free D-serine exclusively occurs in brains,(More)
We compared the activity of free D-Ser on the potentiation of cloned NMDA receptors with that of Gly by using a Xenopus oocyte expression system. The extracellular concentration of free D-Ser and Gly was further studied by means of microdialysis. The ED50 values of D-Ser were three to four times lower than those of Gly in any combination of epsilon 1,(More)
We have examined whether D-amino acid oxidase (DAO) regulates free D-serine content using mutant ddY/DAO- mice lacking DAO activity. We find that the content of D-serine in the serum and cerebellum of mutant mice is much higher than that of normal mice, whereas a slight but significant difference in the cerebral D-serine level is observed between the two(More)
Using an in vivo microdialysis technique, we have measured the extracellular concentration of endogenous free D-serine in comparison with that of L-serine, glycine and L-glutamate in the discrete brain areas of the freely moving rat. A high concentration of D-serine was observed in the dialysate obtained from the medial prefrontal cortex and striatum,(More)
We have analyzed free chiral amino acids (aspartate and serine) in the human frontal cortex at different ontogenic stages (from 14 weeks of gestation to 101 years of age) by HPLC with fluorometric detection after derivatization with N-tert-butyl-oxycarbonyl-L-cysteine and o-phthaldialdehyde. Exceptionally high levels of free D-aspartate and D-serine were(More)
It has long been assumed that L-forms of amino acids exclusively constitute free amino acid pools in mammals. However, a variety of studies in the last decade has demonstrated that free D-aspartate and D-serine occur in mammals and may have important physiological function in mammals. Free D-serine is confined predominantly to the forebrain structure, and(More)
We have investigated the anatomical distribution and postnatal development of D-aspartate and D-serine in the rat brain and periphery using HPLC techniques. D-Serine was confined predominantly to the brain throughout postnatal life. At birth, a substantial quantity of D-serine was observed throughout the brain areas. The cerebral D-serine content increased(More)
The behavioral effects produced by MK-801 (0.4 mg/kg) were compared in mutant DAO-/- mice lacking D-amino acid oxidase activity and normal DAO+/+ mice. Mutant mice display marked diminution of stereotypy and ataxia induced by MK-801 compared to normal mice. Because the D-serine level in the brain of mutant mice is significantly higher than that of normal(More)
To obtain further insight into the distribution and metabolism of exogenous D-serine, we have investigated the effect of the intraperitoneal administration of D-serine (10 mmol/kg) on the concentrations of D- and L-serine in several brain areas and periphery of infant and adult rats. The administration produced a significant augmentation of the D-serine(More)
The behavioral effects induced by methamphetamine (5.0 mg/kg) were compared in the mutant mice lacking d-amino acid oxidase activity and normal mice. The mutant mice exhibited marked decline in the methamphetamine-induced stereotypy compared to the normal mice, whereas the mutant mice displayed a drastic augmentation in the locomotor activity evoked by(More)