| Project/Area Number |
18591274
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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 (70312296)
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| Co-Investigator(Kenkyū-buntansha) |
KASHIWA Atsushi Tokyo Medical and Dental University, Medical Hospital Psychiatry, Assistant Professor (10301227)
KURUMAJI Akeo Tokyo Medical and Dental University, Graduate School Psychiatry and Behavioral Sciences, Associate Professor (00251504)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥3,950,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2007: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2006: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Keywords | D-serine / glutamate / NMDA receptor / schizophrenia / NMDA |
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| Research Abstract |
In this study we have been focusing on the regulation of D-serine metabolism in the mammalian brain and its clinical application for the development of novel treatment of drug-resistant schizophrenic symptoms. Recent investigations by us and others indicated possible involvement of dysfunction of glutamatergic signaling in the pathophysiology of both positive and negative symptoms of schizophrenia D-serine is an endogenous co-agonist of NMDA type glutamate receptors. We have isolated and characterized D-serine-modulator-1 (dsm-1) gene, which may play a crucial role in the regulation of cellular D-serine release in the central nervous system. Also, we determined the effect of glial toxins on the extracellular D-serine concentration of the rat brain. The obtained results implicated that glial cells are much involved in the regulation of D-serine metabolism in the mammalian brain Recent clinical trials for schizophrenia suggested that D-serine, glycine and D-cycloserine, as allosteric agonists of the NMDA receptors should be strong candidates of the novel generation antipsychotics. Curiously, we have found D-cycloserine selectively modulate the extracellular concentration of neural D-serine. Further studies should be able us to understand molecular and cellular mechanism of the regulation of neural D-serine metabolism and the development of novel pharmacotherapy of schizophrenia.
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