SERELAS · FUNCTION AND REGULATION OF D-SERINE RELEASE BY ASTROCYTES IN THE CENTRAL NERVOUS SYSTEM: DEVELOPMENT OF A D-SERINE MICROBIOSENSOR.
6РП — Действия „Мария Кюри“
- Период
- 2005-06-01 → 2007-05-31
- Финансиране от ЕС
- 80 000 €
- Участници
- 1
- Схема
- IRG
Линиите свързват координатора с партньорите.
Накратко на български
D-серинът е химически пратеник в мозъка, чието освобождаване се следи в реално време чрез нов микробиосензор. Разбирането на тези механизми помага при работата с заболявания като шизофрения, епилепсия и инсулти.
Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.
Резултати накратко
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.
Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз
Цел на проекта
The D-enantiomer of the amino acid serine is a novel neural modulator released by glial cells within the central nervous system (CNS). Like glycine, D-serine is a coagonist of the glutamatergic N-methyl-D-aspartate (NMDA) receptor. D-serine is necessary fo r NMDA-receptor activation in the hippocampus and could play a critical role in synaptic plasticity, learning and memory or the pathophysiology of brain ischemia. However, the physiological function and the regulation of D-serine release in the CNS are sti ll poorly understood. Through the development of an original D-serine microsensor, I will measure the extracellular concentration of D-serine in brain slices or in the CNS of freely moving rats. The microsensor will be composed of a carbon fiber covered wi th the enzyme D-amino acid oxidase (D-AAOx). D-AAOx selectively degrades D-serine while producing H2O2 that can be detected by the carbon fiber as an index of the ambient D-serine concentration. Using this microsensor, I will determine the kinetics of D-se rine release and clearance in the CNS and examine the possibility of a functional coupling between neuronal activity and D-serine release by astrocytes. In particular, I will investigate whether stimulation of Schaffer collaterals can evoke the release of D-serine in area CA1 of the hippocampus, and whether D-serine release is correlated with the induction of long-term potentiation. By implanting this microsensor in anesthetized or freely moving rats, I will monitor D-serine release during behavioral tasks such as spatial or emotional learning, and in pathological situations like brain ischemia. Finally, the development of this microsensor will pave the way for the in vivo evaluation of potential drugs aimed at modulating D-serine levels. Overall, this proje ct will help understand the mechanisms and functions of D-serine release in the CNS and contribute to the development of new pharmacological tools targeting D-serine.
Оригинален текст от CORDIS (на английски).
Участници
- CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE · PARISКоординаторФранция
Връзки
Данни: CORDIS, © Европейски съюз