d-Amino acids in rat brain measured by liquid chromatography/tandem mass spectrometry

Previous work has established that d-amino acids including d-serine (d-Ser) and d-aspartic acid (d-Asp) fulfill specific biological functions in the brain. In this work, the levels and anatomical distribution of d-amino acids in rat brain were determined by using an advantageous liquid chromatography/tandem mass spectrometric analytical method. The study was focused on d-Ser, d-Asp, and d-glutamic acid (d-Glu) because of the significance of l-Asp, l-Glu, and d-Ser in the nervous system. Prenatal, postnatal pups, and 90-day old rats were studied. Results indicated that d-Asp and d-Ser occurred in rat brain at the μg/g tissue level. However, d-Glu was not detected (<110 ng/g tissue). Throughout the developmental stages d-Asp content in rat brain decreased rapidly from 9.42% of total Asp in 5-day prenatal rats to an undetectable level (<150 ng/g tissue) in 90-day old rats. In contrast, d-Ser level increased gradually throughout the developmental stages. d-Ser percentage (d-Ser/(d-Ser + l-Ser)) changed from 4.94% in 5-day prenatal rats to 13.7% in 90-day old rats. Regional levels of d-Ser were found to be significantly higher in cortex, striatum, and hippocampus than in thalamus. d-Ser was not detected in cerebellum (<172 ng/g tissue).