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

Abstract

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.