STUDY ON THE D-SERINE METABORISM IN THE BRAIN AND APPLICATION FOR THE TREATMENT OF SCHIZOPHRENIA

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D-Serine is an endogenous agonist of NMDA type glutamale receptor in the mammalian central nervous system. To obtain insight into the origin and metabolic pathway of D-serine at cellular and molecular levels, we have examined the effect of selective destruction of local neuronal cell bodies on the D-serine tissue content. The results suggested that the D-serine content was regulated by local neurons rather than axonal terminals projected from other areas. Interaction between neurons and glial cells might be crucial for the regulation of tissue and extracellular D-serine contents in the central nervous system. We have also isolated a D-serine-regulated transcript, dsr-2 from the rat cerebral neocortex. The dsr-1 was expressed predominantly in the brain, lung and testis. The expression of dsr-1 was significantly and selectively enhanced by D-serine in the cerebral neocortex. Further understanding of the molecular mechanism of endogenous D-serine metabolism in the brain will be important for the development of novel antipsychotic drugs.