Systematic determination of the neuronal circuit underlying depression and elucidation of the mechanism for neuro-glial injury

• Project/Area Number: 25293252
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Psychiatric science
• Research Institution: Kyushu University
• Principal Investigator: KANBA SHIGENOBU 九州大学, 医学(系)研究科(研究院), 教授 (50195187)
• Co-Investigator(Renkei-kenkyūsha): ONITSUKA TOSHIAKI 九州大学, 大学院医学研究院, 准教授 (00398059) ; TAKAHIRO KATO 九州大学, 先端融合医療レドックスナビ, 特任助教 (70546465) ; KEISUKE MOTOMURA 九州大学, 大学病院, 助教 (60432944) ; TOMOFUMI MIURA 九州大学, 大学病院, 助教 (90404053)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥18,070,000 (Direct Cost: ¥13,900,000、Indirect Cost: ¥4,170,000); Fiscal Year 2015: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000); Fiscal Year 2014: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000); Fiscal Year 2013: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
• Keywords: うつ病 / 神経炎症 / 動物モデル / ニューロン・グリア相関

Outline of Final Research Achievements

Based on the neuroinflammation hypothesis of depression, we investigated behavior and brain of the mice which were injected with bacterial endotoxin. Despite of transient activation of the microglia, we could not detect persistent alteration of the marker molecules in the astroglia and oligodendroglia. Minocycline, inhibitor of microglial activation, induced depressive behavior in the tail suspension test in the mice. We also developed a new technique for creating induced microglia-like cells from human peripheral blood. In the MRI study, we accumulated diffuse tensor image of the patients with mood disorder. These results added further information regarding possible interaction between neuroinflammation and depression.

Research Products

• [Journal Article] Direct induction of ramified microglia-like cells from human monocytes: Dynamic microglial dysfunction in Nasu-Hakola disease (2014)
  • Author(s): Ohgidani M, Kato TA*, Setoyama D, Sagata N, Hashimoto R, Shigenobu K, Yoshida T, Hayakawa K, Shimokawa N, Miura D, Utsumi H, Kanba S
  • Journal Title: Scientific Reports Volume: 4 Pages: 4957-4957
• [Journal Article] BDNF induces sustained intracellular Ca2+ elevation through the upregulation of surface TRPC3 channels in rodent microglia (2014)
  • Author(s): Mizoguchi Y*, Kato TA, Seki Y, Ohgidani M, Sagata N, Horikawa H, Yamauchi Y, Sato-Kasai M, Hayakawa K, Inoue R, Kanba S, Monji A
  • Journal Title: Journal of Biological Chemistry Volume: 289(26) Pages: 18549-18555
• [Journal Article] Microglial intracellular Ca2+ signaling as a target of antipsychotic actions for the treatment of schizophrenia (2014)
  • Author(s): Mizoguchi Y*, Kato TA, Horikawa H, Monji A
  • Journal Title: Frontiers in Cellular Neuroscience Volume: 8 Pages: 370-370
• [Journal Article] Genetic dissection of medial habenula–interpeduncular nucleus pathway function in mice (2013)
  • Author(s): 小林 祐樹、 佐野 良威、Vannoni Elizabetta、 後藤 大道、 鈴木 瞳、 大葉 敦子、川崎 弘詔、 神庭 重信、 Lipp Hans-Petter、 Murphy Niall P、 Wolfer David P、 糸原 重美
  • Journal Title: Frontiers in Behavioral Neuroscience Volume: 7
  • DOI: 10.3389/fnbeh.2013.00017
  • Peer Reviewed
• [Journal Article] Mechanism forretardation of amyloid fibril formation by sugars in Va,6 protein. (2013)
  • Author(s): Abe M, Abe Y, Ohkuri T, Mishima T, Monji A, Kanba S, Ueda T.
  • Journal Title: Protein Sci. Volume: 22 Issue: 4 Pages: 467-474
  • DOI: 10.1002/pro.2228
  • Peer Reviewed
• [Journal Article] Immuno-inflammatory, oxidative and nitrosative stress, and neuroprogressive pathways in the etiology, course and treatment of schizophrenia (2013)
  • Author(s): Anderson G, Berk M, Dodd S, Bechter K, Altamura AC, Dell'osso B, Kanba S, Monji A, Fatemi SH, Buckley P, Debnath M, Das UN, Meyer U, Müller N, Kanchanatawan B, Maes M
  • Journal Title: Prog Neuropsychopharmacol Biol Psychiatry Volume: Apr Pages: 1-4
  • DOI: 10.1016/j.pnpbp.2012.10.008
  • Peer Reviewed
• [Journal Article] Neurotransmitters, psychotropic drugs and microglia: clinical implications for psychiatry. (2013)
  • Author(s): Kato TA, Yamauchi Y, Horikawa H, Monji A, Mizoguchi Y, Seki Y, Hayakawa K, Utsumi H, Kanba S
  • Journal Title: Curr Med Chem Volume: 20(3) Pages: 331-44
  • Peer Reviewed
• [Journal Article] Are microglia minding us? Digging up the unconscious mind-brain relationship from a neuropsychoanalytic approach (2013)
  • Author(s): Kato TA, Kanba S
  • Journal Title: Front Hum Neurosci Volume: 13 Pages: 13-13
  • DOI: 10.3389/fnhum.2013.00013
  • Peer Reviewed
• [Journal Article] Missing and Possible Link between Neuroendocrine Factors, Neuropsychiatric Disorders, and Microglia (2013)
  • Author(s): Kato TA, Hayakawa K, Monji A, Kanba S
  • Journal Title: Front Integr Neurosci Volume: Jul 15
  • DOI: 10.3389/fnint.2013.00053
  • Peer Reviewed
• [Presentation] Neuronal correlates of antidepressant effect in the forced swim test in mice. (2013)
  • Author(s): Yanagida S, Motomura K, Ohashi A, Hiraoka K, Kanba S.
  • Organizer: 12th World Congress of Biological Psychiatry
  • Place of Presentation: 京都市
• [Presentation] Prolonged activation of microglia induced by systemic lipopolysaccharide administration in mice. (2013)
  • Author(s): Ohashi A, Motomura K, Yanagida S, Hiraoka K, Kanba S. June 27, 2013, Kyoto, Japan.
  • Organizer: 12th World Congress of Biological Psychiatry
  • Place of Presentation: 京都市
• [Patent(Industrial Property Rights)] Method of producing microglial cells (2015)
  • Inventor(s): Kato TA,Ohgidani M,Kanba S
  • Industrial Property Rights Holder: Kato TA,Ohgidani M,Kanba S
  • Industrial Property Rights Type: 特許
  • Filing Date: 2015-01-09
  • Overseas