| Project/Area Number |
13670987
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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 |
KUBOTA Tetsuo (2002) Tokyo Medical and Dental University, Associate professor, 大学院・保健衛生学研究科, 助教授 (90205138)
岩間 久行 (2001) 東京医科歯科大学, 大学院・医歯学総合研究科, 助手 (00160135)
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| Co-Investigator(Kenkyū-buntansha) |
NISHIKAWA Toru Tokyo Medical and Dental University, Professor, 大学院・医歯学総合研究科, 教授 (00198441)
窪田 哲朗 東京医科歯科大学, 大学院・保健衛生学研究所, 助教授 (90205138)
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| Project Period (FY) |
2001 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2002: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2001: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | Endogenous D-serin / N-Methyl-D-aspartate receptor / Quinolinic acid / Medial frontal cortex / Striatum / Primary culture of hippocampus / Anti-D-serine antibody / Schizophrenia / GABA / ドーパミン / 前頭葉皮質 |
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| Research Abstract |
Using an in vivo dialysis technique, we have studied the extracellular contents of endogenous free D-serine in comparison with that of L-serine, glycine and L-glutamate in the brain of the freely moving rat. A high amount of D-serine was detected in the dialysate obtained from the medial prefrontal cortex and striatum, whereas the cerebellar dialysate contained only a trace concentration of the D-amino acid. Intra-medial prefrontal cortex perfusion of a sodium channel activator, veratrine, augmented the extracellular release of glycine and L-glutamate but a slight decrease in that of D-serine in a tetrodotoxin-sensitive manner in the prefrontal area. Moreover, selective destruction of neuronal cell bodies in the medial frontal region by means of local infusion of an excitotoxin quinolinate resulted in a marked reduction of extracellular and tissue levels of D-serine in the infused prefrontal region. These findings suggest that endogenous Dserine might be liberated into the extracellular space from non-neuronal cells or certain exceptional neuronal cells probably by a carrier-mediated process in the mammalian prefrontal cortex . Also, the endogenous D-amino acid has been indicated to be accumulated or synthesized, at least in part, in the neuronal cells.
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