Basic study in mice to establish a novel screening system of antidepressants.

• Project/Area Number: 19790280
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Experimental pathology
• Research Institution: Tohoku University
• Principal Investigator: KASAHARA Jiro Tohoku University, 大学院・薬学研究科, 講師 (10295131)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥3,620,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥420,000); Fiscal Year 2008: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2007: ¥1,800,000 (Direct Cost: ¥1,800,000)
• Keywords: 脳神経疾患 / 薬理学 / シグナル伝達 / モデル動物 / リン酸化反応 / 細胞内カルシウム

Research Abstract

中枢神経細胞核内に豊富に存在するカルモジュリン依存性キナーゼIV(CaMKIV) をノックアウトしたマウスの、既存抗うつ薬に対する感受性が分子レベル・細胞レベル・個体行動レベルにおいて、野生型マウスと比較して有意に減弱していることを初めて明らかにし、特に大脳皮質前頭領域と辺縁系が関わることが示唆された。また既存の抗うつ薬が関わるセロトニンやノルアドレナリンが、大脳皮質初代培養神経細胞においてCaMKIVなどを活性化して基質である転写因子CREBのリン酸化反応を制御することも明らかにした。

Research Products

• [Journal Article] Cardioprotective effect of vanadyl sulfate on ischemia/reperfusion-induced injury in rat heart in vivo is mediated by activation of protein kinase B and induction of FLICE-inhibitory protein (2008)
  • Author(s): Bhuiyan MS, Takada Y, Shioda N, Moriguchi S, Kasahara J, Fukunaga K
  • Journal Title: Cardiovascular Therapeutics 26 Pages: 10-23
• [Journal Article] Cardioprotective effect of vanadyl sulfate on ischemia/reperfusion-induced injury in rat heart in vivo is mediated by activation of protein kinase B and induction of FLICE-inhibitory protein. (2008)
  • Author(s): Bhuiyan MS, Takada Y, Shioda N, Moriguchi S, Kasahara J, Fukunaga K.
  • Journal Title: Cardiovascular Therapeutics 26 Pages: 10-23
  • Peer Reviewed
• [Journal Article] Reduced CREB phosphorylation after chronic lithium treatment is associated with down-regulation of CaM kinase IV in rat hippocampus (2007)
  • Author(s): Tardito D, Tiraboschi E, Kasahara J. et al.
  • Journal Title: International Journal of Neuropsychopharmacology 10(4) Pages: 491-496
• [Journal Article] Imbalance between CaM kinase II and calcineurin activities impairs caffeine-induced calcium release in hypertrophic cardiomyocytes (2007)
  • Author(s): Lu YM., Shioda N., Han F., Moriguchi S., Kasahara J., Shirasaki Y., Win ZH. and Fukunaga, K
  • Journal Title: Biochemical Pharmacology 74(12) Pages: 1727-1737
• [Journal Article] Cytoprotective effect of bis(1-oxy-2-pyridinethiolato)oxovanadiun(IV) on myocardial ischemia/reperfusion injury elicits inhibition of Fas ligand and Bim expression and elevation of FLIP expression (2007)
  • Author(s): Bhuiyan MS., Shibuya M., Shioda N., Moriguchi S., Kasahara J., Iwabuchi Y. and Fukunaga K
  • Journal Title: European. Journal of Pharmacology 571(203) Pages: 180-188
• [Journal Article] Reduced CREB phosphorylation after chronic lithium treatment is associated with down-regulation of CaM kinase IV in rat hippocampus. (2007)
  • Author(s): Tardito D, Tiraboschi E, Kasahara J., et. al.
  • Journal Title: International Journal of Neuropsychopharmacology. 10(4) Pages: 491-496
  • Peer Reviewed
• [Presentation] バナジウム化合物とメラトニンによるドパミン神経障害の保護効果 (2008)
  • Author(s): 笠原二郎、長井智史、澁谷正俊、荒木令江、岩渕好治、福永浩司
  • Organizer: 第31回神経科学大会
  • Place of Presentation: 東京
  • Year and Date: 2008-07-11
• [Presentation] マウス脳における抗うつ薬慢性投与によるカルモジュリンキナーゼIVの活性化とCREBリン酸化反応 (2008)
  • Author(s): 笠原二郎、阪上洋行、福永浩司
  • Organizer: 第81回日本薬理学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2008-03-17
• [Presentation] マウス脳における抗うつ薬慢性投与によるカルモジュリンキナーゼIVの活性化とCREBリン酸化反応 (2008)
  • Author(s): 笠原二郎、阪上洋行、福永浩司
  • Organizer: 第81回日本薬理学会年会
  • Place of Presentation: 横浜市
  • Year and Date: 2008-03-17
• [Presentation] Requirement of calcium/calmodulin-dependent protein kinase IV (CaMKIV)-activity for the effects of antidepressants in mouse brain (2007)
  • Author(s): Kasahara J., Fukunaga K. and Sakagami H
  • Organizer: Society for Neuroscience 2007
  • Place of Presentation: アメリカ合衆国・サンディエゴ
  • Year and Date: 2007-11-07
• [Presentation] Requirement of calcium/calmodulin-dependent protein kinase IV(CaMKIV)-activity for the effects of antidepressants in mouse brain. (2007)
  • Author(s): Kasahara J., Fukunaga K. and Sakagami H.
  • Organizer: Society for Neuroscience 2007
  • Place of Presentation: アメリカ合衆国・サンディエゴ
  • Year and Date: 2007-11-07
• [Presentation] マウス脳におけるCaMKIV活性は抗うつ薬の効果発現に必要である (2007)
  • Author(s): 笠原二郎、阪上洋行、近藤尚武、福永浩司
  • Organizer: 第73回日本生化学会東北支部会例会
  • Place of Presentation: 仙台
  • Year and Date: 2007-05-12
• [Presentation] マウス脳におけるCaMKIV活性は抗うつ薬の効果発現に必要である (2007)
  • Author(s): 笠原二郎、阪上洋行、近藤尚武、福永浩司
  • Organizer: 第73回日本生化学会東北支部会例会
  • Place of Presentation: 仙台市
  • Year and Date: 2007-05-12