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

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Microelectrode Biosensors

Part of the book series: Neuromethods ((NM,volume 80))

Abstract

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.

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Authors and Affiliations

  1. INSERM U1028, CNRS UMR5292, Lyon Neuroscience Research Center, AniRA-Neurochem Technological Platform, Team WAKE, Lyon, France

    Pierre Pernot & Caroline Maucler

  2. FaUniversité Claude Bernard Lyon 1, Centre de Recherches en Neurosciences de Lyon (CRNL), Inserm U1028, CNRS UMR5292, Lyon, France

    Stéphane Marinesco

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  1. Pierre Pernot
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  2. Caroline Maucler
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  3. Stéphane Marinesco
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  1. Faculté de médecine, CRNL, Université Claude Bernard Lyon I, Avenue Rockefeller 8, Lyon, 69373, France

    Stéphane Marinesco

  2. School of Life Sciences, University of Warwick, Gibbet Hill Road, Coventry, CV4 7AL, United Kingdom

    Nicholas Dale

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Pernot, P., Maucler, C., Marinesco, S. (2013). Regulation of Extracellular Concentrations of d-Serine in the Central Nervous System Revealed by d-Amino Acid Oxidase Microelectrode Biosensors. In: Marinesco, S., Dale, N. (eds) Microelectrode Biosensors. Neuromethods, vol 80. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-62703-370-1_9

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  • DOI: https://doi.org/10.1007/978-1-62703-370-1_9

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