2007 Fiscal Year Final Research Report Summary
Regulation of neural D-serine metabolism and its application for the development of novel treatment of schizophrenia
| 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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| 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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[Journal Article] S1-1 nuclear domains: characterization and dynamics as a function of transcriptional activity.2008
Author(s)
Inoue A, Tsugawa K, Tokunaga K, Takahashi KP, Uni S, Kimura M, Nishio K, Yamamoto N, Hshio K, Yamamoto N, Honda KI, Watanabe T, Yamane, Tani T.:
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Journal Title
Description
「研究成果報告書概要(和文)」より
Peer Reviewed
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[Journal Article] S1-1 nuclear domains : characterization and dynamics as a function of transcriptional activity2008
Author(s)
Inoue A, Tsugawa K, Tokunaga K, Takahashi KP, Uni S, Kimura M, Nishio K, Yamamoto N. Honda KI, Watanabe T, Yamane, Tani T.
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Journal Title
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Study on the regulatory mechanisms of glutamate-D-serine system and the application for the development of new generation antipsychotics. (Japanese)2007
Author(s)
Yamamoto N, Shimazu D, Umino A, Ishii S, Sakurai S, Taniguchi G, Kozuka N, Kaneko Y, Takebayashi H, Sato J, Kanematsu S, Kashiwa A, Kurumaji A, Nishikawa T
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Journal Title
Annual Report of Pharmaco-psychiatry Research 39
Pages: 22-27
Description
「研究成果報告書概要(欧文)」より
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