Study on the mechanism of neural D-serine metabolism and application for the pharmacotherapeutics of schizophrenia
| Project/Area Number |
16591125
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Psychiatric science
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
YAMAMOTO Naoki Tokyo Medical and Dental University, Medical Hospital, Psychiatry, Assistant Professor, 医学部附属病院, 講師 (70312296)
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| Co-Investigator(Kenkyū-buntansha) |
KASHIWA Atsushi Tokyo Medical and Dental University, Graduate School, Psychiatry and Behavioral Sciences, Research Associate, 大学院・医歯学総合研究科, 助手 (10301227)
INOUE Akira Osaka City University, Graduate School of Medicine, Molecular Mechanisms of Biological Regulation, Associate Professor, 大学院・医学研究科, 助教授 (50109857)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2005: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2004: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | D-serine / glutamate / NMDA receptor / schizophrenia |
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| Research Abstract |
Regulation of NMDA receptor function by the modulation of endogenous D-serine in the central nervous system has been considered to be one of the crucial target pathways for the development of novel treatment of antipsychotics-resistant schizophrenia. In this study, we have been characterized molecular mechanisms that regulate D-serine metabolism in the mammalian brain. In first, using Xenopus oocyte expression cloning system, we have isolated D-serine modulator-1 (dsm-1), which regulates uptake and release of extracellular D-serine in the brain. Characterization of biochemical kinetics and distribution of dsm-1 suggested the dsm-2 gene product can be one of the molecular targets for the drug-screening of novel antipsychotics. In second, by differential screening, we have isolated D-serine responsive transcript-2 (dsr-2). The distribution of dsr-2 was closely related to endogenous D-serine and NMDA receptor NR2B subtype in the central nervous system. Genomic structure and the developmentally regulated localization of dsr-2 together suggested that dsr-2 gene product is involved in the D-serine metabolism and function. These findings and further study should provide us an insight to understand the mechanism of D-serine metabolism in the brain and possible molecular targets for the development of antischizophrenic drugs.
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Report
(3 results)
Research Products
(25 results)
