Molecular mechanism of D-serine for pathophysiology of schizophrenia

• Project/Area Number: 22390220
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Psychiatric science
• Research Institution: Chiba University
• Principal Investigator: HASHIMOTO Kenji 千葉大学, 社会精神保健教育研究センター, 教授 (10189483)
• Co-Investigator(Renkei-kenkyūsha): IYO Masaomi 千葉大学, 大学院・医学研究院, 教授 (50191903) ; MORI Hisashi 富山大学, 大学院・医学薬学研究部(医学), 教授 (00239617)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥17,680,000 (Direct Cost: ¥13,600,000、Indirect Cost: ¥4,080,000); Fiscal Year 2012: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2011: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000); Fiscal Year 2010: ¥7,020,000 (Direct Cost: ¥5,400,000、Indirect Cost: ¥1,620,000)
• Keywords: 統合失調症 / D型セリン / NMDA受容体 / D型サイクロセリン / セリンラセマーゼ / D型アミノ酸 / D型アミノ酸酸化酵素 / グルタミン酸受容体

Research Abstract

D-serine in the brain is known to be synthesized from serine racemase (SRR). In the methamphetamine model of schizophrenia, we found that methamphetamine-induced behavioral sensitization was not detected in the SRR knock-out mice. This study suggests that SRR plays a role in the development of behavioral sensitization by methamphetamine treatment.

Research Products

• [Journal Article] Glutamate modulators as potential therapeutic drugs in schizophrenia and affective disorders (2013)
  • Author(s): Hashimoto, K., Malchow, B., Falkai, P., and Schmitt, A
  • Journal Title: Eur. Arch. Psychiatry Clin. Neurosci Volume: (in press) Issue: 5 Pages: 367-377
  • DOI: 10.1007/s00406-013-0399-y
  • Peer Reviewed
• [Journal Article] Is D-cycloserine a prodrug forD-serine in the brain? Biol (2013)
  • Author(s): Horio, M., Mori, H., and Hashimoto, K
  • Journal Title: Psychiatry Volume: (in press) Issue: 12 Pages: e33-e34
  • DOI: 10.1016/j.biopsych.2012.07.013
  • Peer Reviewed
• [Journal Article] Neonatal disruption of serine racemase causes schizophrenia-like behavioral abnormalities in adulthood: Clinical rescue by D-serine (2013)
  • Author(s): Hagiwara, H., Iyo, M., and Hashimoto, K
  • Journal Title: PLoS One Volume: 8
  • Peer Reviewed
• [Journal Article] Decreased levels of D-aspartic acid in the forebrain of serine racemase (Srr) knock-out mice (2013)
  • Author(s): Horio, M., Ishima, T., Fujita, Y., Inoue, R., Mori, H., and Hashimoto, K
  • Journal Title: Neurochem. Int Volume: 62 Issue: 6 Pages: 843-847
  • DOI: 10.1016/j.neuint.2013.02.015
  • Peer Reviewed
• [Journal Article] Role of serine racemase in behavioral sensitization in mice after repeated administration of methamphetamine (2012)
  • Author(s): Horio, M., Kohno, M., Fujita, Y., Ishima, T., Inoue, R., Mori, H., and Hashimoto, K
  • Journal Title: PLoS One Volume: 7 Issue: 4 Pages: e35494-e35494
  • DOI: 10.1371/journal.pone.0035494
  • Peer Reviewed
• [Journal Article] Levels of D-serine in the brain and peripheral organs of serine racemase (Srr) knock-out mice (2011)
  • Author(s): Horio, M., Kohno, M., Fujita, Y., Ishima, T., Inoue, R., Mori, H., and Hashimoto, K
  • Journal Title: Neurochem. Int Volume: 59 Issue: 6 Pages: 853-859
  • DOI: 10.1016/j.neuint.2011.08.017
  • Peer Reviewed
• [Journal Article] Magnetic resonance spectroscopy study of the antioxidant defense system in schizophrenia (2011)
  • Author(s): Matsuzawa D, Hashimoto K
  • Journal Title: Antioxidants & Redox Signaling Volume: 15 Issue: 7 Pages: 2057-2065
  • DOI: 10.1089/ars.2010.3453
  • Peer Reviewed
• [Journal Article] Levels of D-serine in the brain and periphery organs of serine racemase (Srr) knock-out mice (2011)
  • Author(s): Horio M, et al.
  • Journal Title: Neurochemistry International Volume: 59 Pages: 853-859
  • Peer Reviewed
• [Journal Article] Comments to"The effect of risperidone on D-amino acid oxidase activity as a hypothesis for a novel mechanism of action in the treatment of schizophrenia" (2010)
  • Author(s): K.Hashimoto
  • Journal Title: J.Psychopharmacol. Volume: 24 Pages: 1133-1134
  • Peer Reviewed
• [Journal Article] Analyses of mechanism for mouse strain-dependent prepulse inhibition point toarole of Shmtl(SHMTI)in mice and schizophrenia. (2010)
  • Author(s): T.Maekawa, et al.
  • Journal Title: J.Neurochem. Volume: 115 Pages: 1374-1385
  • Peer Reviewed
• [Presentation] Therapeutic effects of metabotropic glutamate receptor 5positive allosteric modulator CDPPB on phencyclidine-induced cognitive deficits in mice (2012)
  • Author(s): Hashimoto, K., Horio, M., and Fujita, Y
  • Organizer: 22^<nd> Neuropharmacology Conference "Cognitive Enhancers"
  • Place of Presentation: New Orleans, USA
• [Presentation] D-サイクロセリンは、脳においてD-セリンのプロドラッグか? (2012)
  • Author(s): 堀尾菜央、森寿、橋本謙二
  • Organizer: 第8回D-アミノ酸研究会学術講演会
  • Place of Presentation: 滋賀県大津市
• [Presentation] D－サイクロセリンは、脳においてD-セリンのプロドラッグか？ (2012)
  • Author(s): 堀尾菜央（橋本謙二）
  • Organizer: 第8回D-アミノ酸研究会学術講演会
  • Place of Presentation: 滋賀県大津市
  • Invited
• [Presentation] ペンチレンテトラゾール誘発痙攣発作におけるDセリンの機能解析 (2011)
  • Author(s): 井上蘭, ら
  • Organizer: 第7回D-アミノ酸研究会学術講演会
  • Place of Presentation: 東京都
  • Year and Date: 2011-09-10
• [Presentation] Lack of behavioral sensitization in serine racemase knock-out mice after administration of methamphetamine (2011)
  • Author(s): Horio, M., Fujita, Y., Kohno, M., Inoue, R., Mori, H., and Hashimoto, K
  • Organizer: The 41th Annual Meeting of Society for Neuroscience
  • Place of Presentation: Washington DC, USA
• [Presentation] セリンラセマーゼ遺伝子欠損マウスでの覚せい剤投与による行動感作の欠如 (2011)
  • Author(s): 堀尾菜央、河野眞美、藤田有子、井上蘭、森寿、橋本謙二
  • Organizer: 第7回D-アミノ酸研究会学術講演会
  • Place of Presentation: 東京都
• [Presentation] Lack of behavioral sensitization in serine racemase knock-out mice after administration of methamphetamine (2011)
  • Author(s): Horio M, et al.
  • Organizer: The 41th Annual Meeting of Society for Neuroscience
  • Place of Presentation: 米国ワシントンDC市
• [Presentation] セリンラセマーゼ遺伝子欠損マウスの脳および末梢臓器におけるDセリン濃度 (2010)
  • Author(s): 堀尾菜央, ら
  • Organizer: 第6回D-アミノ酸研究会学術講演会
  • Place of Presentation: 富山市
• [Book] The Handbook of Behavior, Diet and Nutrition (2011)
  • Author(s): K.Hashimoto
  • Publisher: Springer Publishers In press
• [Remarks]
  • URL: http://www.m.chiba-u.ac.jp/class/shakai/jp/index.html
• [Remarks]
  • URL: http://www.m.chiba-u.ac.jp/class/shakai/jp/byoutai/index.html
• [Remarks]
  • URL: http://www.m.chiba-u.ac.jp/class/shakai/jp/byoutai/index.html