Effect of the intracerebroventricular and systemic administration of L-serine on the concentrations of D- and L-serine in several brain areas and periphery of rat

To gain further insight into the metabolic mechanism of endogenous D-serine, the effect of the intracerebroventricular and intraperitoneal administration Of L-serine on the concentrations Of D- and L-serine in several brain areas and periphery was investigated. The intracerebroventricular injection Of L-serine caused a rapid and marked increase in the L-serine levels in almost all brain regions of adult rats. This administration also produced a gradual increase in the D-serine levels in the forebrain, whereas a slight but significant elevation Of D-serine was found in the cerebellum and pons-medulla. The intraperitoneal administration Of L-serine caused a marked increase in the L-serine levels in all brain regions of both infant and adult rats. The treatment induced a significant augmentation of the D-serine levels in all brain regions of infant rats with higher concentrations in the cerebellum and cortex, whereas no significant change was observed in the cerebellum and pons-medulla of adult rats. These in vivo observation, together with the fact that immunohistochemical studies have indicated that both D-serine and serine racemase are highly concentrated in Bergmann glia of developing cerebellum, suggest that D-serine can be synthesized not only in the forebrain but also in the hindbrain by serine racemase. Furthermore, because the drastic decline in the cerebellar D-serine level coincides well with a dramatic increase in the cerebellar D-amino acid oxidase during early postnatal development, synthesized D-serine may be metabolized by D-amino acid oxidase in the hindbrain of adult rats. (C) 2002 Elsevier Science B.V. All rights reserved.