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Final Activity Report Summary - SERELAS (Function and regulation of D-Serine release by astrocytes in the central nervous system: Development of a D-Serine microbiosensor)

D-serine is an important chemical messenger between neurons and glial cells in the brain. Malfunction in the D-serine system has been implicated in several neurological and psychiatric pathologies including stroke, epilepsy, brain tumours or schizophrenia. In particular, D-serine has been administered to schizophrenic patients in conjunction with well-known antipsychotic drugs to ameliorate the efficacy of current treatments. However, the mechanisms of D-serine regulation in the central nervous system are still poorly understood. The goal of this project was to develop a microbiosensor that can be implanted in the brain of laboratory animals to detect D-serine release in situ and in real time. This microbiosensor is made of a platinum fibre microelectrode covered by a layer of the polymer poly-m-phenylenediamine and by an additional membrane of the enzyme D-amino acid oxidase. D-serine is specifically recognized by the biosensor, and produces an electrical current of intensity proportional to its concentration in the medium. This microbiosensor is sensitive enough to detect low D-serine levels present in the brain and responds within 1-2 seconds to rapid changes in concentration. This method has been validated using brain extracts; it provides accurate and selective estimation of D-serine levels confirmed with well-known chromatographic techniques.

The D-serine microbiosensor was then implanted in the brain of anesthetised rats. It detected D-serine diffusion into the brain following a peripheral injection, and revealed large differences in D-serine diffusion between the cortex, the cerebellum and the ventricles. Pharmacological compounds susceptible to modulate D-serine transmission are currently being evaluated using this technique. These data further our understanding of the regulation of D-serine levels in the brain and pave the way for improvements in pharmacological treatments of schizophrenia based on D-serine administration in humans.

Overall, this project has allowed the development of a D-serine microbiosensor that can be implanted in the central nervous system of laboratory animals, in order to better understand the pathophysiological functions of D-serine in the brain.