Analysis of D-serine dynamics in the brain and development of novel drugs against excitotoxicity

2015 Fiscal Year Final Research Report

• Project/Area Number: 25293059
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: General pharmacology
• Research Institution: University of Toyama
• Principal Investigator: Mori Hisashi 富山大学, 大学院医学薬学研究部(医学), 教授 (00239617)
• Co-Investigator(Kenkyū-buntansha): TOYOOKA Naoki 富山大学, 大学院理工学研究部(工学), 教授 (10217565)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: D-セリン / セリンラセマーゼ / マウスモデル / 興奮性神経毒性 / 創薬

Outline of Final Research Achievements

In this study, we have tried to reveal the roles of D-serine in the neural functions and dysfunctions and examined the roles of D-serine producing enzyme serine racemase (SR) in vivo. We have found the novel roles of SR and D-serine in D-aspartate production, pain regulation in the spinal chord, and barrier function in the skin. Furthermore, to analyze the molecular basis of D-serine dynamics regulation in the brain, we have tried to generate two new mouse models, 1) neuronal D-serine transporter (Asc-1) conditional knockout mouse and 2) astrocyte-selective expression of D-serine degradation enzyme (Dsd-1) in mouse.
We also developed a novel SR inhibitor which is effective to suppress over-excitation in the brain. This compound will be a lead drug expected to suppress neuronal excitotoxicity.

Free Research Field

分子神経科学