Decreased levels of free D-aspartic acid in the forebrain of serine racemase (Srr) knock-out mice

D-Serine, an endogenous co-agonist of the N-methyl-D-aspartate (NMDA) receptor is synthesized from L-serine by serine racemase (SRR). A previous study of Srr knockout (Srr-KO) mice showed that levels of D-serine in forebrain regions, such as frontal cortex, hippocampus, and striatum, but not cerebellum, of mutant mice are significantly lower than those of wild-type (WT) mice, suggesting that SRR is responsible for D-serine production in the forebrain. In this study, we attempted to determine whether SRR affects the level of other amino acids in brain tissue. We found that tissue levels of D-aspartic acid in the forebrains (frontal cortex, hippocampus and striatum) of Srr-KO mice were significantly lower than in WT mice, whereas levels of D-aspartic acid in the cerebellum were not altered. Levels of D-alanine, L-alanine, L-aspartic acid, taurine, asparagine, arginine, threonine, gamma-amino butyric acid (GABA) and methionine, remained the same in frontal cortex, hippocampus, striatum and cerebellum of WT and mutant mice. Furthermore, no differences in D-aspartate oxidase (DDO) activity were detected in the forebrains of WT and Srr-KO mice. These results suggest that SRR and/or D-serine may be involved in the production of D-aspartic acid in mouse forebrains, although further detailed studies will be necessary to confirm this finding. (C) 2013 Elsevier Ltd. All rights reserved.