Neural mechanisms underlying stress vulnerability -involvement of neurogenesis in mood disorder

2013 Fiscal Year Final Research Report

• Project/Area Number: 23591667
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Psychiatric science
• Research Institution: Hokkaido University
• Principal Investigator: NAKAGAWA shin 北海道大学, 大学病院, 講師 (60360905)
• Co-Investigator(Kenkyū-buntansha): INOUE Takshi 北海道大学, 大学院医学研究科, 准教授 (70250438) ; BOKU Shuken 北海道大学, 大学院医学研究科, 助教 (60455665)
• Project Period (FY): 2011 – 2013
• Keywords: 神経細胞新生 / うつ病 / 抗うつ薬 / 気分安定薬 / ドパミン / グリア細胞 / CaMKIV / 気分障害

Research Abstract

In this study we took particular note of neurogenesis in the adult hippocampus as molecular basis of stress vulnerability in the brain, and investigated the regulatory mechanisms of it. In vivo and vitro studies showed that dopamine increased neurogenesis via D1 receptors. Although antidepressants have been known to increase neurogenesis, we showed the new pathways including glia with FGF-2 and CaMKIV-CREB. In addition, anti-apoptotic effect and its mechanisms of mood stabilizers in the hippocampal progenitor cells were found. All these findings will contribute to make novel therapeutic drugs against mood disorder.

Research Products

• [Journal Article] The effect of dopamine on adult hippocampal neurogenesis (2014)
  • Author(s): Takamura N, Nakagawa S, Masuda T,Boku S, Kato A, Song N, An Y, Kitaichi Y, Inoue T, Koyama T, Kusumi I
  • Journal Title: Prog Neuropsychopharmacol Biol Psychiatry Volume: 50 Pages: 116-124
  • DOI: 10.1016/j.pnpbp.2013.12.011
  • Peer Reviewed
• [Journal Article] Valproate recovers the inhibitory effect of dexamethasone on the proliferation of the adult dentate gyrus-derived neural precursor cells via GSK-3β and β-catenin pathway (2014)
  • Author(s): Boku S, Nakagawa S, Masuda T,Nishikawa H, Kato A, Takamura N, Omiya Y, Kitaichi Y, Inoue T, Kusuimi I
  • Journal Title: Eur J Pharmacol Volume: 15 Pages: 425-430
  • DOI: 10.1016/j.ejphar.2013.10.060
  • Peer Reviewed
• [Journal Article] Tricylic antidepressant amitriptyline indirectly increases the proliferation of adult dentate gyrus-derived neural precursors : and involvement of astrocytes (2014)
  • Author(s): Boku S, Hisaoka-Nakashima K,Nakagawa S, Kato A, Kajitani N, Inoue T, Kusumi I, Takebayashi M
  • Journal Title: PLoS One Volume: 50 Pages: 116-124
  • DOI: 10.1371/journal.pone.0079371
  • Peer Reviewed
• [Journal Article] GDNF facilitates differentiation of the adult dentate gyrus-derived neural precursor cells into astrocytes via STAT3 (2013)
  • Author(s): Boku S, Nakagawa S, Takamura N,Kato A, Takebayashi M, Hisaoka-Nakashima K, Omiya Y,Inoue T, Kusumi I
  • Journal Title: Biochem. Biophys Res Commun Volume: 434 Pages: 779-784
  • DOI: 10.1016/j.bbrc.2013.04.011
  • Peer Reviewed
• [Journal Article] ROCK2 regulatesbFGF-induced proliferation of SH-SY5Y cells through GSK-3β and β-catenin pathway (2013)
  • Author(s): Boku S, Nakagawa S, Toda H, Kato A,Takamura N, Omiya Y, Inoue T, Koyama T
  • Journal Title: Brain Res Volume: 1492 Pages: 7-17
  • DOI: 10.1016/j.brainres.2012.11.034
  • Peer Reviewed
• [Journal Article] Involvement of CaMKIV in neurogenic effect with chronic fluoxetine treatment (2013)
  • Author(s): Song N, Nakagawa S, Izumi T, Toda H,Kato A, Boku S, Inoue T, Sakagami H, Li X B, Koyama T
  • Journal Title: Int J Neuropsychopharmacol Volume: 16 Pages: 803-812
  • DOI: 10.1017/S1461145712000570
  • Peer Reviewed
• [Journal Article] Mood stabilizers commonly restorestaurosporine-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 Volume: 38 Pages: 183-189
  • DOI: 10.1016/j.pnpbp.2012.03.006
  • 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
  • DOI: 10.1016/j.pnpbp.2011.08.019
  • 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 H, Kato A, Toda H, Song N, Kitaichi Y, Inoue T, Koyama T
  • Journal Title: Prog Neuropsychopharmacol Biol Psychiatry Volume: 35 Pages: 111-117
  • DOI: 10.1016/j.pnpbp.2010.09.019
  • Peer Reviewed
• [Presentation] Involvement of CaMKIV in antidepressant action (2013)
  • Author(s): Nakagawa. S, Song. N, Takamura. N,Kato. A, An. Y, Inoue. T, Li. X, Kusumi. I
  • Organizer: 43th Annual Meeting Society for Neuroscience
  • Place of Presentation: Convention Center (San Diego, USA)
  • Year and Date: 20131109-13
• [Presentation] Effect of dopamine on adulthippocampal neurogenesis (2013)
  • Author(s): Nakagawa. S, Takamura. N, Boku. S,Song. N, Kato. A, Inoue. T, Kusumi. I
  • Organizer: 第11回世界生物学的精神医学会国際会議
  • Place of Presentation: 国立京都国際会館(京都市)
  • Year and Date: 20130623-27
• [Presentation] Effect of dopamine on adult hippocampal neurogenesis (2012)
  • Author(s): Nakagawa. S, Takamura. N, Boku. S,Song. N, Kato. A, Inoue. T
  • Organizer: 42th Annual Meeting Society for Neuroscience
  • Place of Presentation: New Orleans Convention Center (New Orleans,USA)
  • Year and Date: 20121013-17
• [Presentation] Involvement of CaM kinase IV in the action of antidepressant treatment (2011)
  • Author(s): Nakagawa. S, Song. N, Izumi. T,Boku. S, Toda. H, Kato. A, Li. X, Inoue.T, Sakagami. H, Koyama. T
  • Organizer: 41th Annual Meeting Society for Neuroscience
  • Place of Presentation: Washington DCConvention Center (Washington DC,USA)
  • Year and Date: 20111112-16
• [Book] うつ病—治療・研究の最前線 医学のあゆみ 別冊 (2014)
  • Author(s): 中川 伸、井上 猛、橋本謙二、功刀 浩
  • Total Pages: 512 (465-470)
  • Publisher: 医歯薬出版株式会社
• [Book] 専門医のための精神科リュミエール (2011)
  • Author(s): 中川 伸、小山 司
  • Total Pages: 345 (68-76)
  • Publisher: 中山書店 (27)
• [Book] Depression. Neurogenesis in the adult brain II (2011)
  • Author(s): Nakagawa S and Duman RS (Edited by Seki T, Sawamoto K, Parent JM and Alvarez-Buylla A)
  • Total Pages: 210 (99-108)
  • Publisher: Springer, Tokyo