Free D-serine in post-mortem brains and spinal cords of individuals with and without neuropsychiatric diseases.

We have measured the concentrations of free D-serine post-mortem in the prefrontal cortex, parietal cortex, cerebellum and spinal cord from individuals with and without (controls) neuropsychiatric diseases using high-performance liquid chromatography with fluorometric detection. The levels of D-serine were found to be high in the prefrontal and parietal cortex (around 100 nmol/g wet weight) and very low in the cerebellum and spinal cord (below 10 nmol/g wet weight). The uneven distribution of the D-amino acid in the human central nervous system (CNS) resembles that observed in rodents, suggesting that, as shown in the rat CNS, the regional variation of D-serine content in the human brain might also be closely correlated with those of the N-methyl-D-aspartate (NMDA) type excitatory amino acid receptor. In the prefrontal cortex, the gray and white matter had a similar concentration of D-serine. These 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 be an intrinsic modulator of the NMDA receptor liberated from certain glial cells in the mammalian brain. Despite the anti-psychotogen activity of D-serine in the rat, there were no statistically significant differences between the D-serine contents in the prefrontal or parietal cortex of controls and those of patients with schizophrenia or dementia of the Alzheimer type.