FREE D-SERINE IN POSTMORTEM BRAINS AND SPINAL-CORDS OF INDIVIDUALS WITH AND WITHOUT NEUROPSYCHIATRIC DISEASES

We have measured the concentrations of free D-serine post-mortem in th e prefrontal cortex, parietal cortex, cerebellum and spinal cord from individuals with and without (controls) neuropsychiatric diseases usin g high-performance liquid chromatography with fluorometric detection. The levels of D-serine were found to be high in the prefrontal and par ietal cortex (around 100 nmol/g wet weight) and very low in the cerebe llum and spinal cord (below 10 nmol/g wet weight). The uneven distribu tion of the D-amino acid in the human central nervous system (CNS) res embles that observed in rodents, suggesting that, as shown in the rat CNS, the regional variation of D-serine content in the human brain mig ht also be closely correlated with those of the N-methyl-D-aspartate ( NMDA) type excitatory amino acid receptor. In the prefrontal cortex, t he gray and white matter had a similar concentration of D-serine. Thes e findings, together with the selective action of D-serine at the NMDA -related glycine site and the non-neurogenic nature of extracellular D -serine release, add further support to the view that D-serine could b e an intrinsic modulator of the NMDA receptor liberated from certain g lial cells in the mammalian brain. Despite the anti-psychotogen activi ty of D-serine in the rat, there were no statistically significant dif ferences between the D-serine contents in the prefrontal or parietal c ortex of controls and those of patients with schizophrenia or dementia of the Alzheimer type.