Establishment of new therapy for the perinatal depression syndrome by regulation of adult hippocampal neurogenesis.

• Project/Area Number: 22500291
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Neuroscience in general
• Research Institution: Osaka University
• Principal Investigator: KITABATAKE Yasuji 大阪大学, 医学系研究科, 助教 (80506494)
• Co-Investigator(Renkei-kenkyūsha): OTA Akemi 大阪大学, 医学系研究科・小児科, 特任研究員 (20283799)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2012: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2011: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2010: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: うつ病 / 海馬 / 神経新生

Research Abstract

Although major depression is one of the leading causes of morbidity, its mechanisms are not well understood. Here we identified a Wnt signaling inhibitor, secreted frizzled-related protein 3 (sFRP3), as a molecular target of antidepressant treatments in rodent models. Neuronal activity decreases the expression of secreted sFRP3, and sFRP3 deletion activates various step of neurogenesis in the adult mouse hippocampus. Furthermore, in tail-suspension and forced-swimming tests, which are reliable predictors of antidepressant potential, sFRP3 knockout mice showed significantly reduced levels of immobility compared to WT animals. Our studies identify a novel function of sFRP3 as an essential mediator of antidepressant actions in animal models. Targeting of sFRP3 may represent a novel therapeutic approach for depression treatment.

Research Products

• [Journal Article] Secreted frizzled-related protein 3 regulates activity-dependent adult hippocampal neurogenesis (2013)
  • Author(s): Jang M-H*, Bonaguidi M*, Kitabatake Y*, Sun J*, Song J, Kang E, Jun H, Zhong C, Su Y, Guo J, Wang M, Sailor K, Kim J-Y, Gao Y, Christian K, Ming G-l and Song H
  • Journal Title: Cell Stem Cell Volume: 12 Pages: 215-23
• [Journal Article] Secreted Frizzled-related Protein 3 (sFRP3) regulates antidepressant responses in mice and humans (2013)
  • Author(s): Jang M-H*, Kitabatake Y*, Kang E, Jun H, Pletnikov M.V, Christian M, Hen R, Lucae S, Binder E, Song H and Ming G-l
  • Journal Title: Molecular psychiatry Volume: 1 Pages: 1-2
  • DOI: 10.1038/mp.2012.158
  • Peer Reviewed
• [Journal Article] Secreted frizzled-related protein 3 regulates activity-dependent adult hippocampal neurogenesis (2013)
  • Author(s): Mi-Hyeon Jang, Michael A. Bonaguidi, Yasuji Kitabatake
  • Journal Title: Cell Stem Cell Volume: 12 Pages: 215-213
  • DOI: 10.1016/j.stem.2012.11.021
  • Peer Reviewed
• [Journal Article] Chordin-induced lineage plasticity of adult SVZ neuroblasts after demyelination (2010)
  • Author(s): Jablonska B, Aguirre A, Raymond M, Szabo G, Kitabatake Y, Sailor K, Ming G, Song H, Gallo V
  • Journal Title: Nat Neursci Volume: 13 Pages: 541-550
• [Presentation] 海馬神経新生を介した抗うつ薬の作用メカニズムの解明 (2011)
  • Author(s): 北畠康司
  • Organizer: 第2回産と学をつなぐSENRIの会
  • Place of Presentation: 大阪府豊中市千里ライフサイエンスセンター
  • Year and Date: 2011-12-02