title: Decreased levels of free D-aspartic acid in the forebrain of serine racemase (Srr) knock-out mice.
abstract: 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, γ-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.
authors: Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, Chiba, Japan.
authors: Mao
authors: M
authors: Horio
authors: Tamaki
authors: T
authors: Ishima
authors: Yuko
authors: Y
authors: Fujita
authors: Ran
authors: R
authors: Inoue
authors: Hisashi
authors: H
authors: Mori
authors: Kenji
authors: K
authors: Hashimoto
mesh_terms: D000409:Alanine / Q000378:metabolism; D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D001923:Brain Chemistry / Q000235:genetics; D002851:Chromatography, High Pressure Liquid; D050804:D-Aspartate Oxidase / Q000378:metabolism; D026603:D-Aspartic Acid / Q000378:metabolism*; D007668:Kidney / Q000201:enzymology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016548:Prosencephalon / Q000378:metabolism*; D019998:Racemases and Epimerases / Q000235:genetics* / Q000502:physiology*; D000099300:Serine Racemase
chemical_list: D000409:Alanine; D000596:Amino Acids; D050804:D-Aspartate Oxidase; D026603:D-Aspartic Acid; D019998:Racemases and Epimerases; D000099300:Serine Racemase