Regulation of Extracellular Concentrations of d-Serine in the Central Nervous System Revealed by d-Amino Acid Oxidase Microelectrode Biosensors

d- serine is an endogenous co-agonist of N -methyl d -aspartate receptors, and has been implicated in several neurological and psychiatric disorders. Correspondingly, d -serine signaling may represent an important pharmacological target for treating these diseases. However, the biochemical mechanisms that control extracellular concentrations of d -serine in vivo remain unclear. Therefore, we have developed biosensors to monitor d -serine levels in vivo. These biosensors are cylindrical platinum microelectrodes that have been coated with a layer of poly-m -phenylenediamine and then a membrane of immobilized d -amino acid oxidase (DAAO) obtained from the yeast, Rhodotorula gracilis . Using these microelectrode biosensors, extracellular levels of d -serine in the rat frontal cortex were investigated. d -serine was detected in micromolar concentrations in the interstitial fluid, and was observed to diffuse slowly through the blood–brain barrier following peripheral administration of d -serine. By coupling these biosensor measurements with HPLC analysis of whole tissue d -serine contents, we have showed that intracellular stores represent more than 99 % of the total brain d -serine contents. Therefore, the development of DAAO microelectrode biosensors has already improved our ability to understand d -serine regulation in vivo, and holds great potential for future studies.