Alterations in Plasma Levels of Amino Acids after Intracerebroventricular Administration of L-Serine or D-Serine in Conscious and Freely Moving Rats

Abstract

L-Serine has a role in cellular proliferation, being a precursor for protein synthesis, and is also important for brain development. D-Serine plays a role as the endogenous co-agonist at the glycine site on the N-methyl-D-aspartate (NMDA) receptors in the brain. Accumulating evidence suggests that abnormality of D-serine levels might be involved in the pathophysiology of schizophrenia. Using the automated blood sampling system, we examined whether or not intrac- erebroventricular (icv) infusion of L- and D-isomers of serine could affect plasma levels of amino acids in conscious and freely moving rats. The icv infusion of L-serine significantly decreased the plasma levels of glycine, glutamate, and D- serine, but not glutamine and L-serine. Furthermore, the icv infusion of D-serine significantly decreased the plasma levels of glycine, glutamate, and L-serine, but not glutamine. Expectedly, a marked increase of plasma D-serine was detected af- ter icv infusion of D-serine. These findings suggest that the metabolic pathway for L- and D-serine may be markedly dif- ferent in the rat brain. L-Serine has been shown to play a role in cellular prolif- eration, as it is a precursor for nucleotide synthesis (15-17). In addition, after the first reports of serine deficiency disor- ders (3-phosphoglycerate dehydrogenase (3-PGDH) defi- ciency and 3-phosphoserine phosphatase (3-PSP) defi- ciency)), it also became clear that L-serine and L-serine- derived metabolites are important for brain development and function (17-25). In contrast, D-serine, an isomer of L- serine, plays a role as a key co-agonist for NMDA receptors (26-32). D-Serine is produced by serine racemase (SRR) from L-serine, and D-serine has been shown to be metabo- lized by D-amino acid oxidase (DAAO) in the brain. Several