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2002 Fiscal Year Final Research Report Summary

Functional analysis and expression cloning of D-serine uptake site

Research Project

Project/Area Number 12680761
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Neurochemistry/Neuropharmacology
Research InstitutionTokai University

Principal Investigator

HASHIMOTO Atsushi  Tokai University, School of Medicine, Assistant Professor, 医学部, 講師 (80271592)

Project Period (FY) 2000 – 2002
KeywordsD-amino acid / D-serine / uptake site
Research Abstract

Although D-amino acids have been assumed to be unnatural in mammals, a wide variety of studies has demonstrated that free D-serine and serine racemase occur in the mammalian brain. To gain an insight into the uptake site of D-serine, we have investigated the effect of systemic administration of D-serine on the concentrations of D- and L-serine in the several brain areas and periphery of infant and adult rat. Intraperitoneal administration of D-serine caused a drastic increase in the levels of D-serine in all brain areas and periphery of infant and adult rat. The increase in the D-serine levels were higher in the cerebellum and kidney, which D-amino acid oxidase appear during early postnatal development. A systemic injection of D-serine produced a slight but significant increase in the levels of L-serine in almost all brain and peripheral tissues of infant rat. The increase in the L-serine levels might be due to the reverse reaction of serine racemase. Following a systemic injection of D-serine, the D-serine concentrations in all brain areas of adult rat rapidly increased, and peaked at 3 or 6 hours. The D-serine levels in the cortex, striatum, hippocampus, diencephalon gradually decreased and returned to the control levels 7 days after the injection, whereas the D-serine levels in the pons-medulla and cerebellum rapidly decreased and returned to the control levels 3 days after the injection. Because D-serine potentiates the NMDA receptor-mediated neurotransmission via the glycine site with an affinity similar to glycine and because D-serine application ameliorates the positive and negative symptoms of schizophrenia, D-serine administration could be beneficial in treating diseases related to the hypofunction of the NMDA-mediated neurotransmission such as schizophrenia and Alzheimer's disease.

  • Research Products

    (4 results)

All Other

All Publications (4 results)

  • [Publications] Atsushi Hashimoto: "Effects on N-methytl-D-aspartate, kainate or veratridine on"Brain Research Bulletin. 53. 347-351 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Atsushi Hashimoto: "Effect of the intracerebroventricular and systemic"Brain Research. 955. 214-220 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Atsushi Hashimoto: "Effects on N-methyl-D-aspartate, kainate or veratridine on extracellular concentrations of free D-serine and L-glutamate in rat striatum: An in vivo microdlalysis study"Brain Research Bulletin. 53. 347-351 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Atsushi Hashimoto: "Effect of the intracerebro-ventricular and systemic administration of L-serine on the concentrations of D- and L-serine in several brain areas and periphery of rat"Brain Research. 955. 214-220 (2002)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2004-04-14  

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