Mechanisms of stress response relating to medication for depressive disorder focused on microglia

• Project/Area Number: 15K19731
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Psychiatric science
• Research Institution: Hiroshima University
• Principal Investigator: Yamawaki Yosuke 広島大学, 医歯薬保健学研究院(歯), 助教 (90584061)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2016: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 炎症 / ストレス脆弱性 / ミクログリア / うつ病様行動 / PRIP / 中枢炎症 / グリア細胞 / 摂食行動 / サイトカイン / うつ病

Outline of Final Research Achievements

The objective of this study is to elucidate the roles of phospholipase C-related catalytically inactive protein in psychological stress and inflammation-induced depression-like behavior, including anorexia focusing on microglia. Prip-deficient mice showed the vulnerability against LPS-induced anorexia. We revealed that PRIP inhibits AKT-IKK signaling in hypothalamic microglia and regulates the expression of pro-inflammatory cytokines in microglia communicating with astrocyte, which contributes to maintaining the CNS environment.

Research Products

• [Journal Article] Phospholipase C-related catalytically inactive protein can regulate obesity, a state of peripheral inflammation. (2017)
  • Author(s): Yamawaki Y, Oue K, Shirawachi S, Asano S, Harada K, Kanematsu T.
  • Journal Title: Japanese Dental Science Review Volume: 53（1） Issue: 1 Pages: 18-24
  • DOI: 10.1016/j.jdsr.2016.06.001
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] General anesthetic actions on GABAA receptors in vivo are reduced in phospholipase C-related catalytically inactive protein knockout mice. (2017)
  • Author(s): Hayashiuchi M, Kitayama T, Morita K, Yamawaki Y, Oue K, Yoshinaka T, Asano S, Harada K, Kang Y, Hirata M, Irifune M, Okada M, Kanematsu T.
  • Journal Title: Journal of Anesthesia Volume: in press Issue: 4 Pages: 531-538
  • DOI: 10.1007/s00540-017-2350-2
  • Peer Reviewed / Open Access
• [Journal Article] Phospholipase C-related catalytically inactive protein-knockout mice display increased induction of uncoupling protein 1 in adipose tissues following chronic cold exposure. (2017)
  • Author(s): Kana Oue, Yosuke Yamawaki, Satoshi Asano, Mizokami Akiko, Masato Hirata, Masahiro Irifune, Takashi Kanematsu.
  • Journal Title: Journal of Oral Biosciences Volume: 印刷中 Issue: 2 Pages: 108-112
  • DOI: 10.1016/j.job.2017.04.001
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Immobilization stress-induced anorexia is mediated independent of MyD88. (2016)
  • Author(s): Hosoi T, Yamawaki Y, Kimura H, Ozawa K
  • Journal Title: Neuroreport Volume: 27 Issue: 13 Pages: 947-7
  • DOI: 10.1097/wnr.0000000000000641
  • Peer Reviewed
• [Journal Article] Phospholipase C-related catalytically inactive protein is a new modulator of thermogenesis promoted by β-adrenergic receptors in brown adipocytes (2015)
  • Author(s): Kana Oue, Jun Zhang, Kae Harada-Hada, Satoshi Asano, Yosuke Yamawaki, Masaki Hayashiuchi, Hisako Furusho, Takashi Takata, Masahiro Irifune, Masato Hirata, Takashi Kanematsu
  • Journal Title: Journal of Biological Chemistry Volume: 291 Issue: 8 Pages: 4185-96
  • DOI: 10.1074/jbc.m115.705723
  • Peer Reviewed / Open Access / Int'l Joint Research
• [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
• [Presentation] PRIPによる脳内炎症が誘発する摂食抑制行動の調節 (2016)
  • Author(s): 山脇洋輔, 白輪地聡美、兼松隆
  • Organizer: 第58回歯科基礎医学会学術大会
  • Place of Presentation: 北海道
  • Year and Date: 2016-08-24
• [Presentation] Phospholipase C-related catalytically inactive protein is involved in the neuroinflammation-induced anorexia (2016)
  • Author(s): Yosuke Yamawaki, Satomi Shirawachi, Takashi Kanematsu
  • Organizer: CINP 2016
  • Place of Presentation: Seoul, Korea
  • Year and Date: 2016-07-03
  • Int'l Joint Research
• [Presentation] Gene expression analysis in microglia related in antidepressant-like effect of sodium butyrate (2015)
  • Author(s): 山脇洋輔, 兼松隆
  • Organizer: 第57回 歯科基礎医学会
  • Place of Presentation: 新潟
  • Year and Date: 2015-09-11
• [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: CINP Dublin Thematic Meeting
  • Place of Presentation: Dublin / Ireland
  • Year and Date: 2015-06-04
  • Int'l Joint Research