Abstract
A wide variety of evidence has indicated that a high level of D-serine occurs in the mammalian brain. D-serine is predominantly concentrated in the forebrain, where the NMDA receptors are enriched. Because D-serine potentiates the NMDA receptor-mediated transmission by selective stimulation of the glycine site of the NMDA receptor, D-serine has been proposed as an endogenous coagonist for the NMDA receptor-associated glycine site in the mammalian brain. Serine racemase (SRR) that catalyzes the direct formation of D-serine from L-serine and D-amino acid oxidase (DAO) that catalyzes the oxidative deamination of neutral D-amino acids have been cloned from the mammalian brain. Several lines of evidence have demonstrated that the distribution of SRR and those of the D-serine and NMDA receptors share a similar regional pattern, whereas a regional distribution of DAO inversely correlates with both those of D-serine and SRR. Immunohistochemical studies at a cellular level have demonstrated that SRR and DAO were localized exclusively in GFAP-positive astrocytes. Recently, Wolosker's group and we revealed, however, the presence of D-serine and SRR in not only astrocytes but also neurons of rat brain. Because D-serine has been shown to improve the negative, positive and cognitive symptoms of schizophrenic subjects treated with conventional neuroleptics and because SRR and DAO have recently shown to be associated with the susceptibility to schizophrenia, SRR and DAO could play an important role in the regulation of the NMDA receptors via the D-serine metabolism and in the pathogenesis of schizophrenia. [J Physiol Sci. 2007;57 Suppl:S10]
