| Project/Area Number |
24390280
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Partial Multi-year Fund |
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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 |
Nishikawa Toru 東京医科歯科大学, 医歯(薬)学総合研究科, 教授 (00198441)
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| Co-Investigator(Renkei-kenkyūsha) |
KURUMAJI Akeo 東京医科歯科大学, 大学院医歯学総合研究科, 教授 (00251504)
YANAMOTO Naoki 東京医科歯科大学, 医学部附属病院, 講師 (70312296)
JITOKU Daisuke 東京医科歯科大学, 大学院医歯学総合研究科, 助教 (10613854)
UEZATO Akihito 東京医科歯科大学, 大学院医歯学総合研究科, 助教 (90547449)
Takeuchi Takashi 東京医科歯科大学, 医学部附属病院, 講師 (70345289)
KYONO Hoshu 東京医科歯科大学, 医学部附属病院, 助教 (70615658)
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| Project Period (FY) |
2012-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥18,070,000 (Direct Cost: ¥13,900,000、Indirect Cost: ¥4,170,000)
Fiscal Year 2014: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2013: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2012: ¥7,800,000 (Direct Cost: ¥6,000,000、Indirect Cost: ¥1,800,000)
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| Keywords | グルタミン酸伝達 / NMDA受容体 / D-セリン / 難治性抑うつ状態 / NMDA受容体グリシン調節部位 / 内側前頭葉皮質 / キラルアミノ酸分析 / In vivo ダイアリシス / アミノ酸分析 / In vivoダイアリシス / ドーパミン代謝 / 行動変化 |
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| Outline of Final Research Achievements |
On the basis of NMDA receptor blocking action of ketamine that has been reported to show fast-ameliorating effects on refractory depression, the molecular and cellular mechanisms underlying signaling of a NMDA receptor co-agonist, D-serine, have been investigated to obtain a clue for a novel antidepressant. It is indicated that D-serine synthesizing enzyme, serine racemase, Dsm-1 protein which modifies the tissue and extracellular contents of D-serine and zinc ion may modify the extracellular concentrations of D-serine and/or glutamate that acts on the NMDA receptor. Therefore, the three or related molecules could be candidate targets for development of a novel antidepressant that possesses an inhibitory influence on the NMDA receptor. An open-labeled clinical trial of ifenprodil, a NMDA receptor subunit antagonist (GRIN2B), has been initiated.
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