Exploration of the new therapeutic target molecule for treatmentresistant mood disorders through elucidation of the molecular mec hanism of adult hippocampal neurogenesis

• Project/Area Number: 22791102
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Psychiatric science
• Research Institution: Hokkaido University
• Principal Investigator: BOKU Syuken 北海道大学, 北海道大学病院, 助教 (60455665)
• Project Period (FY): 2010 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2011: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2010: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 気分障害 / 成体海馬神経細胞新生 / FGF / GSK-3β / β-catenin / ROCK

Research Abstract

We have already shown that ROCK2 is involved in DEX-induced decrease of bFGF-induced proliferation of adult rat dentate gyrus-derived neural precursor cells(ADP) through regulating he activity of GSK3βand that bFGF and DEX reciprocally regulate the expression of ROCK2. Therefore, ROCK2 may play a role in adult neurogenesis in dentate gyrus. However, it remains unclear whether ROCK2 actually regulate in vivo neurogenesis in adult dentate gyrus. Here we examined the expression of ROCK2 in adult dentate gyrus with in situ hybridization. In addition, we tried to prepare the overexpression system of ROCK2 with retroviral vector and lentiviral vector.

Research Products

• [Journal Article] Involvement of CaMKIV in neurogenic effect with chronic fluoxetine treatment (2012)
  • Author(s): Song N, Nakagawa S, Izumi T, Toda H, Kato A, Boku S, Inoue T, Sakagami H, Li X, Koyama T
  • Journal Title: Int J Neuropsychopharmacology Volume: (in press)
  • Peer Reviewed
• [Journal Article] Mood stabilizers commonly restore staurosporine-induced increase of p53 expression and following decrease of Bcl-2 expression in SH-SY5Y cells (2012)
  • Author(s): Song N, Boku S, Nakagawa S, Kato A, Toda H, Takamura N, Omiya Y, Kitaichi Y, Inoue T, Koyama T
  • Journal Title: Prog Neuropsychopharmacol Biol Psychiatry, Epub ahead of print
  • Peer Reviewed
• [Journal Article] Noradrenaline increases neural precursor cells derived from adult rat dentate gyrus through beta2 receptor (2012)
  • Author(s): Masuda T, Nakagawa S, Boku S, Nishikawa H, Takamura N, Kato A, Inoue T, Koyama T
  • Journal Title: Prog Neuropsychopharmacol Biol Psychiatry Volume: 36 Pages: 44-51
  • Peer Reviewed
• [Journal Article] Effects of combined treatment with clorgyline and selegiline on extracellular noradrenaline and serotonin levels. Acta Neuropsychiatr (2012)
  • Author(s): Kitaichi Y, Inoue T, Nakagawa S, Boku S and Koyama T
  • Journal Title: Accepted manuscript online Volume: (in press) Issue: 6 Pages: 369-373
  • DOI: 10.1111/j.1601-5215.2012.00652.x
  • Peer Reviewed
• [Journal Article] prevents the anxiolytic-like effect of citalopram in rat contextual conditioned fear stress model (2012)
  • Author(s): Masuda T, Nishikawa H, Inoue T, Toda H, Nakagawa S, Boku S, Koyama T
  • Journal Title: Acta Neuropsychiatr. Accepted manuscript online Volume: 25 Issue: 2 Pages: 77-84
  • DOI: 10.1111/j.1601-5215.2012.00669.x
  • Peer Reviewed
• [Journal Article] Sertraline treatment of patients with major depressive disorder who failed initial treatment with paroxetine or fluvoxamine (2012)
  • Author(s): Inoue T, Honda M, Kawamura K, Tsuchiya K, Suzuki T, Ito K, Matsubara R, Shinohara K, Ishikane T, Sasaki K, Boku S, Fujisawa D, Ono Y, Koyama T
  • Journal Title: Prog Neuropsychopharmacol Biol Psychiatry Pages: 22504727-22504727
  • Peer Reviewed
• [Journal Article] Mood stabilizers commonly restore staurosporine-induced increase of p53 expression and following decrease of Bcl-2 expression in SH-SY5Y cells (2012)
  • Author(s): Song N, et al.
  • Journal Title: Prog Neuropsychophamacol Biol Psychiatry Volume: (in press) Issue: 2 Pages: 183-189
  • DOI: 10.1016/j.pnpbp.2012.03.006
  • Peer Reviewed
• [Journal Article] Effects of mood stabilizers on adult dentate gyrus-derived neural precursor cells (2011)
  • Author(s): Boku S, Nakagawa S, Masuda T, Nishikawa S, Kato A, Toda H, Song N, Kitaichi Y, Inoue T, Koyama T
  • Journal Title: Prog Neuropsychopharmacol Biol Psychiatry Volume: 35 Pages: 111-117
  • Peer Reviewed
• [Journal Article] Olanzapine augmentation of milnacipran for stage 2 treatment-resistant major depression an open study (2011)
  • Author(s): Boku S, Inoue T, Honma H, Matsubara S, Nakagawa S, Koyama T
  • Journal Title: Hum Psychopharmacol Volume: 26 Pages: 237-241
  • Peer Reviewed
• [Journal Article] Retrieval of conditioned fear activates the basolateral and intercalated nucleus of amygdala (2011)
  • Author(s): Izumi T, Boku S, Shinmin W, Inoue T, Konno K, Yamaguchi T, Yoshida T, Matsumoto M, Watanabe M, Koyama T, Yoshioka M
  • Journal Title: J Neurosci Res Volume: 89(5) Pages: 773-790
  • Peer Reviewed
• [Journal Article] Olanzapine augmentation of milnacipran for stage 2 treatment-resistant major depression (2011)
  • Author(s): Boku S, Inoue T, Honma H, et al
  • Journal Title: Hum Psychopharmacol Volume: 26 Issue: 3 Pages: 237-241
  • DOI: 10.1002/hup.1197
  • Peer Reviewed
• [Journal Article] Long-term naturalistic follow-up of lithium augmentation : Relevance to bipolarity (2011)
  • Author(s): Inoue T, Abekawa T, Nakagawa S, Suzuki K, Tanaka T, Kitaichi Y, Boku S, Nakato Y, Toda H, Koyama T
  • Journal Title: J Affect Disord Volume: 129 Issue: 1-3 Pages: 64-67
  • DOI: 10.1016/j.jad.2010.08.022
  • Peer Reviewed
• [Journal Article] Effects of mood stabilizers on adult dentate gyrus-derived neural precursor cells (2011)
  • Author(s): Boku S, Nakagawa S, Masuda T, et al
  • Journal Title: Progress in Neuro-Psychopharmacology and Biological Psychiatry Volume: 35 Pages: 111-117
  • Peer Reviewed
• [Journal Article] Sertraline increases extracellular levels not only of serotonin, but also of dopamine in the nucleus accumbens and striatum of rats (2010)
  • Author(s): Kitaichi Y, Inoue T, Nakagawa S, Boku S, Kakuta A, Izumi T, Koyama T
  • Journal Title: Eur J Pharmacol Volume: 647 Pages: 90-96
  • Peer Reviewed
• [Journal Article] Glucocorticoids and Lithium in Adult Hippocampal Neurogenesis (2010)
  • Author(s): Boku S, Nakagawa S, Koyama T
  • Journal Title: Vitamins and Hormones Volume: 82 Pages: 421-431
  • Peer Reviewed
• [Presentation] Involvement of CaM kinase IV in the action of antidepressant treatment (2011)
  • Author(s): Shin Nakagawa, Ning Song, Takeshi Izumi, Shuken Boku, Hiroyuki Toda, Akiko Kato, Xiaobai Li, Takeshi Inoue, Hiroyuki Sakagami, Tsukasa Koyama
  • Organizer: Society for Neuroscience 41th annual meeting
  • Place of Presentation: Walter E.Washington Convention Center (USA)
  • Year and Date: 2011-11-12
• [Presentation] Rho-associated coiled-coil kinase (ROCK2) regulates bFGF-induced proliferation of SH-SY5Y cells through GSK-3β and β-catenin pathway (2011)
  • Author(s): Boku S, et al.
  • Organizer: Society for Neuroscience 41th annual meeting
  • Place of Presentation: Walter E.Washington Convention Center (USA)
  • Year and Date: 2011-11-12
• [Presentation] 抗うつ薬未服用のうつ病患者における脳拡散テンソル画像 (2011)
  • Author(s): 中川伸、Khin Khin Tha、井上猛、仲唐安哉、北川信樹、賀古勇輝、戸田裕之、朴秀賢、亀山梨絵、寺江聡、小山司
  • Organizer: 第30回躁うつ病の薬理・生化学的研究懇話会
  • Place of Presentation: 京都ガーデンパレス(京都)
  • Year and Date: 2011-07-17
• [Presentation] Rho-associated coiled-coil kinase(ROCK2) regulates bFGF-induced proliferation of SH-SY5Y cells through GSK-3βandβ-catenin pathway (2011)
  • Author(s): Boku S, Nakagawa S, Toda H, et al
  • Organizer: Society for Neuroscience 41^<th> annual meeting
  • Place of Presentation: Washington DC
• [Presentation] 気分安定薬はSH-SY5Y細胞においてstaurosporineによるp53の発現増加およびBcl-2の発現減少を抑制させる (2011)
  • Author(s): 朴秀賢、宋寧、中川伸、加藤亜紀子、高村直樹、戸田裕之、井上猛、小山司
  • Organizer: 第30回躁うつ病懇話会
  • Place of Presentation: 京都(ガーデンホテル京都)
• [Presentation] Effects of mood stabilizers on adult dentate gyrus-derived neural precursor cells (2010)
  • Author(s): Shuken Boku
  • Organizer: 第25回韓国生物学的精神医学会
  • Place of Presentation: ソウル・リッツカールトンホテル(韓国)(招待講演)
  • Year and Date: 2010-10-01
• [Book] 気分安定薬と成体海馬歯状回神経細胞新生.気分障害の薬理・生化学-総括と新たなる挑戦- (2012)
  • Author(s): 朴秀賢
  • Publisher: 医薬ジャーナル