EMBRYONIC-DEVELOPMENT AND POSTNATAL CHANGES IN FREE D-ASPARTATE AND D-SERINE IN THE HUMAN PREFRONTAL CORTEX

We have analyzed free chiral amino acids (aspartate and serine) in the human frontal cortex at different ontogenic stages (from 14 weeks of gestation to 1 01 years of age) by HPLC with fluorometric detection af ter derivatization with N-tert-butyl-oxycarbonyl-L-Cysteine and o-phth aldialdehyde. Exceptionally high levels of free D-aspartate and D-seri ne were demonstrated in the fetal cortex at gestational week 14. The r atios of D-aspartate and of D-serine to the total corresponding amino acids were also high, at 0.63 and 0.27, respectively. The concentratio n of D-aspartate dramatically decreased to a trace level by gestationa l week 41 and then remained very low during all postnatal stages. In c ontrast, the frontal tip contained persistently high levels of D-serin e throughout embryonic and postnatal life, whereas the D-amino acid co ntent in adolescents and aged individuals was about half of that in th e fetuses. Because D-aspartate and D-serine are known to have selectiv e actions at the NMDA-type excitatory amino acid receptor, the present data suggest that these D-amino acids might play a pivotal role in ce rebral development and functions that are related to the NMDA receptor .