Research of microglial epigenetics as a mechanism of constructing stress vulnerability

• Project/Area Number: 25861036
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Psychiatric science
• Research Institution: Hiroshima University (2014); Hiroshima International University (2013)
• Principal Investigator: YAMAWAKI YOSUKE 広島大学, 医歯薬保健学研究院(歯), 助教 (90584061)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: うつ病 / ストレス脆弱性 / ミクログリア / エピジェネティクス / HDAC阻害薬 / 精神疾患 / 炎症 / グリア / 炎症性サイトカイン

Outline of Final Research Achievements

The object of this study is to elucidate a mechanism of stress vulnerability from a view of neuro-immune system. Treatment of lipopolysaccharide (5 mg/kg, i.p.) induced persisting microglial activation in hippocampus and elongated immobility time in forced swim test (FST). Repeated treatment with sodium butyrate (SB), HDAC inhibitor, inhibited the LPS-induced microglial activation and decreased the immobility time in FST. cDNA Microarray using isolated hippocampal microglia treated with LPS and/or SB revealed the several candidate genes, relating to regulating macrophage function, immune system and mechanism of antidepressant.

Research Products

• [Journal Article] The potential use of histone deacetylase inhibitors in the treatment of depression (2015)
  • Author(s): Fuchikami M, Morinobu S, et al.
  • Journal Title: Progress in Neuro-Psychopharmacology & Biological Psychiatry Volume: 62 Pages: 00059-7
  • DOI: 10.1016/j.pnpbp.2015.03.010
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Possible involvement of rumination in gray matter abnormalities in persistent symptoms of major depression: An exploratory magnetic resonance imaging voxel-based morphometry study. (2014)
  • Author(s): Machino, A., Kunisato, Y., Matsumoto, T., Yoshimura, S., Ueda, K., Yamawaki, Y., ... & Yamawaki, S.
  • Journal Title: Journal of Affective Disorders Volume: 168 Pages: 229-235
  • DOI: 10.1016/j.jad.2014.06.030
  • Peer Reviewed
• [Presentation] Sodium butyrate ameliorates inflammation-induced depression-like behavior via inhibition of microglial activation (2015)
  • Author(s): Yosuke Yamawaki, Norika Yoshioka, Misako Nishida, Ayaka Murai, Takashi Kanematsu, Hiroyuki Akagi
  • Organizer: CINP2015
  • Place of Presentation: ダブリン/英国
  • Year and Date: 2015-06-03 – 2015-06-05
• [Presentation] ミクログリア抑制効果に基づくHDAC阻害薬の抗うつ効果の検討 (2015)
  • Author(s): 山脇洋輔、吉岡伯華、西田美沙子、村井彩佳、吉野貴成、赤木宏行
  • Organizer: 日本薬学会 第135年会
  • Place of Presentation: 神戸
  • Year and Date: 2015-03-25 – 2015-03-28
• [Presentation] 酪酸ナトリウムによる炎症誘発性うつ病様行動の改善効果 (2015)
  • Author(s): 山脇 洋輔, 吉岡 伯華, 西田 美沙子, 村井 彩佳, 大植 香菜, 林内 優樹, 兼松 隆, 赤木 宏行
  • Organizer: 第88回 日本薬理学会年会
  • Place of Presentation: 名古屋
  • Year and Date: 2015-03-18 – 2015-03-20