Investigation of the glutamate hypothesis for schizophrenia using iPS cells

• Project/Area Number: 15K19728
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Psychiatric science
• Research Institution: Kobe University
• Principal Investigator: Mouri Kentaro 神戸大学, 医学研究科, 助教 (00642125)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2016: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 臨床精神分子遺伝学

Outline of Final Research Achievements

The KIF17 gene plays an important role in transport of NMDA receptors . We found that a missense SNP of KIF17 was significantly higher in schizophrenia group on the relationship between KIF 17. The protein expression of KIF17 in schizophrenic postmortem brains was significantly less than that in controls. We knocked down KIF17 gene in mouse neural progenitor cells (mNPCs) and the proliferation ability of the mNPCs was evaluated but no significant change was observed. In astrocytes treated with clozapine , KIF 17 mRNA expression were significantly decreased . For iPS cells derived from human, since it was possible to establish a system of induction of differentiation from human iPS cells to neurons, we will continue to analyze the influence on differentiation after continuing operations such as suppressing the expression of KIF17 gene .

Research Products

• [Journal Article] Association study of MIF promoter polymorphisms with suicide completers in the Japanese population (2017)
  • Author(s): Naofumi Shimmyo, Akitoyo Hishimoto, Ikuo Otsuka, Satoshi Okazaki, Shuken Boku, Kentaro Mouri, Tadasu Horai, Motonori Takahashi, Yasuhiro Ueno, Osamu Shirakawa, Ichiro Sora
  • Journal Title: Neuropsychiatric Disease and Treatment Volume: 13 Pages: 899-908
  • DOI: 10.2147/ndt.s130855
  • NAID: 120006024452
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] The cell cycle-related genes as biomarkers for schizophrenia. (2016)
  • Author(s): Okazaki S, Boku S, Otsuka I, Mouri K, Aoyama S, Shiroiwa K, Sora I, Fujita A, Shirai Y, Shirakawa O, Kokai M, Hishimoto A.
  • Journal Title: Prog Neuropsychopharmacol Biol Psychiatry Volume: 70 Pages: 85-91
  • DOI: 10.1016/j.pnpbp.2016.05.005
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] A decrease in protein level and a missense polymorphism of KIF17 are associated with schizophrenia. (2015)
  • Author(s): Ratta-Apha W, Mouri K, Boku S, Ishiguro H, Okazaki S, Otsuka I, Sora I, Arinami T, Shirakawa O, Hishimoto A.
  • Journal Title: Psychiatry Res. Volume: 230 Issue: 2 Pages: 424-429
  • DOI: 10.1016/j.psychres.2015.09.031
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Association analysis of the HLA-DRB1*01 and HLA-DRB1*04 with schizophrenia by tag SNP genotyping in the Japanese population. (2015)
  • Author(s): Ratta-apha W, Boku S, Mouri K, Okazaki S, Otsuka I, Watanabe Y, Nunokawa A, Someya T, Shirakawa O, Sora I, Hishimoto A.
  • Journal Title: Psychiatry Res. Volume: 229 Issue: 1-2 Pages: 627-628
  • DOI: 10.1016/j.psychres.2015.07.016
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Association analysis of the Cadherin13 gene with schizophrenia in the Japanese population. (2015)
  • Author(s): Otsuka I, Watanabe Y, Hishimoto A, Boku S, Mouri K, Shiroiwa K, Okazaki S, Nunokawa A, Shirakawa O, Someya T, Sora I.
  • Journal Title: Neuropsychiatr Dis Treat. Volume: 11 Pages: 1381-1393
  • DOI: 10.2147/ndt.s84736
  • NAID: 120005657654
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant