Involvement of Cxcl12/Cxcr4 signaling deficits in schizophrenia

• Project/Area Number: 26293074
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Pathological medical chemistry
• Research Institution: Research Institute, Shiga Medical Center
• Principal Investigator: Tanigaki Kenji 滋賀県立成人病センター(研究所), 神経病態研究部門, 専門研究員 (70362473)
• Project Period (FY): 2014-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥15,990,000 (Direct Cost: ¥12,300,000、Indirect Cost: ¥3,690,000); Fiscal Year 2017: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2016: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2015: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2014: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
• Keywords: 統合失調症 / Cxcr4 / Cxcl12 / ケモカイン / SDF1 / 22q11 deletion syndrome / Dgcr8 / Schizophrenia / lymphoblastoid cell line / EBV / lymphoblastoid cell / schizophrenia / 脳神経疾患 / miRNA / 神経発生 / 22q11欠損症候群 / NMDAR / PPI

Outline of Final Research Achievements

22q11 deletion syndrome is a chromosome disorder. 20-30% of the patients with this deletion develop schizophrenia. We previously showed that the heterozygous deletion of Dgcr8 caused Cxcl12/Cxcr4 signaling deficits, leading to developmental abnormalities in the dentate gyrus of the hippocampus and interneruons. In this study, we examined whether Cxcl12/Cxcr4 signal deficits can cause schizophrenia-like behavioral abnormalities using Cxcr4-floxed mice, and whether Cxcl12/Cxcr4 signal deficits exist in sporadic schizophrenia patients using lymphodblastic cell lines.

Research Products

• [Int'l Joint Research] Johns Hopkins University(米国)
• [Journal Article] Copy number elevation of 22q11.2 genes arrests the developmental maturation of working memory capacity and adult hippocampal neurogenesis. (2018)
  • Author(s): Boku S, Izumi T, Abe S, Takahashi T, Nishi A, Nomaru H, Naka Y, Kang G, Nagashima M, Hishimoto A, Enomoto S, Duran-Torres G, Tanigaki K, Zhang J, Ye K, Kato S, Männistö PT, Kobayashi K, Hiroi N.
  • Journal Title: Mol Psychiatry. Volume: 23 Issue: 4 Pages: 985-992
  • DOI: 10.1038/mp.2017.158
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Preparation of Robust Metal-Free Magnetic Nanoemulsions Encapsulating Low-Molecular-Weight Nitroxide Radicals and Hydrophobic Drugs Directed Toward MRI-Visible Targeted Delivery. (2017)
  • Author(s): Nagura K, Takemoto Y, Moronaga S, Uchida Y, Shimono S, Shiino A, Tanigaki K, Amano T, Yoshino F, Noda Y, Koizumi S, Komatsu N, Kato T, Yamauchi J, Tamura R.
  • Journal Title: Chemistry. Volume: 23 Pages: 15713-15720
  • Peer Reviewed
• [Journal Article] Regulation of striatal dopamine responsiveness by Notch/RBP-J signaling. (2017)
  • Author(s): Toritsuka M, Kimoto S, Muraki K, Kitagawa M, Kishimoto T, Sawa A, Tanigaki K.
  • Journal Title: Transl Psychiatry. Volume: 7 Issue: 3 Pages: e1049-e1049
  • DOI: 10.1038/tp.2017.21
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Sex-related difference in human white matter volumes studied: Inspection of the corpus callosum and other white matter by VBM. (2017)
  • Author(s): Shiino A, Chen YW, Tanigaki K, Yamada A, Vigers P, Watanabe T, Tooyama I, Akiguchi I.
  • Journal Title: Sci Rep Volume: 7 Issue: 1 Pages: 39818-39818
  • DOI: 10.1038/srep39818
  • Peer Reviewed / Open Access
• [Journal Article] Polymorphism within a Neuronal Activity-Dependent Enhancer of NgR1 Is Associated with Corpus Callosum Morphology in Humans (2015)
  • Author(s): Isobe M, Tanigaki K, Muraki K, Miyata J, Takemura A, Sugihara G, Takahashi H, Aso T, Fukuyama H, Hazama M, Murai T
  • Journal Title: Mol Neuropsychiatry Volume: 1 Issue: 2 Pages: 105-115
  • DOI: 10.1159/000430463
  • Peer Reviewed
• [Journal Article] Arsenic trioxide sensitizes glioblastoma to a myc inhibitor. (2015)
  • Author(s): Yoshimura Y, Shiino A, Muraki K, Fukami T, Yamada S, Satow T, Fukuda M, Saiki M, Hojo M, Miyamoto S, Onishi N, Saya H, Inubushi T, Nozaki K, Tanigaki.
  • Journal Title: Plos One Volume: 10 Issue: 6 Pages: e0128288-e0128288
  • DOI: 10.1371/journal.pone.0128288
  • NAID: 120005947136
  • Peer Reviewed / Open Access
• [Journal Article] Neuronal migration abnormalities and its possible implications for schizophrenia. (2015)
  • Author(s): Kazue Muraki, Kenji Tanigaki
  • Journal Title: Front Neurosci. Volume: 9 Pages: 74-74
  • DOI: 10.3389/fnins.2015.00074
  • Peer Reviewed / Open Access
• [Journal Article] 遺伝子研究と統合失調症 (2014)
  • Author(s): 谷垣健二
  • Journal Title: 精神科 Volume: 25 Pages: 593-597
• [Presentation] Regulation of Striatal Dopamine Responsiveness by Notch/RBP-J Signaling (2017)
  • Author(s): Kenji Tanigaki
  • Organizer: 第40回日本分子生物学会年会
• [Presentation] 22q11欠損症候群モデルマウスにおける介在神経細胞移動の異常 (2015)
  • Author(s): 谷垣健二
  • Organizer: 第38回日本分子生物学会
  • Place of Presentation: 神戸
  • Year and Date: 2015-12-01
  • Invited
• [Presentation] Deficits in microRNA-mediated Cxcr4/Cxcl12 signaling in neurodevelopmental deficits in a 22q11-deletion syndrome mouse model. (2015)
  • Author(s): Kenji Tanigaki
  • Organizer: 第38回神経科学会
  • Place of Presentation: 神戸
  • Year and Date: 2015-07-30
  • Invited
• [Presentation] Comt-mediated regulation of GABAergic system in a 22q11 deletion syndrome model mice. (2014)
  • Author(s): 谷垣健二
  • Organizer: 日本神経化学会
  • Place of Presentation: 奈良
  • Year and Date: 2014-10-01
  • Invited
• [Remarks] 滋賀県立成人病センター 研究所
  • URL: http://www.shigamed.jp/index.html