統合失調症におけるミクログリア制御異常による白質・シナプス伝達障害の機構解明

• Project Area: Glial assembly: a new regulatory machinery of brain function and disorders
• Project/Area Number: 25117011
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
• Research Institution: Kyushu University
• Principal Investigator: 神庭 重信 九州大学, 医学研究院, 教授 (50195187)
• Project Fiscal Year: 2013-06-28 – 2018-03-31
• Project Status: Granted(Fiscal Year 2016)
• Budget Amount: ¥51,090,000 (Direct Cost : ¥39,300,000、Indirect Cost : ¥11,790,000); Fiscal Year 2016 : ¥13,650,000 (Direct Cost : ¥10,500,000、Indirect Cost : ¥3,150,000); Fiscal Year 2015 : ¥13,650,000 (Direct Cost : ¥10,500,000、Indirect Cost : ¥3,150,000); Fiscal Year 2014 : ¥13,650,000 (Direct Cost : ¥10,500,000、Indirect Cost : ¥3,150,000); Fiscal Year 2013 : ¥10,140,000 (Direct Cost : ¥7,800,000、Indirect Cost : ¥2,340,000)
• Keywords: ミクログリア / 統合失調症 / 炎症免疫仮説 / ミノサイクリン / トランスレーショナル研究 / 再生医学 / オリゴデンドロサイト / グリアアセンブリ / 抗精神病薬

Outline of Annual Research Achievements

統合失調症におけるグリア仮説、特にミクログリア仮説を検証するために、モデル動物を用いた実験に加えて、ヒト血液由来直接誘導ミクログリア様細胞（iMG細胞）を用いたトランスレーショナル研究を実施している。Cuprizone投与モデルマウスにおいて、海馬におけるミクログリア活性化を認め、特定の薬剤が活性化制御することを見出しており、現在、論文投稿中である。

Current Status of Research Progress

Research has progressed on the whole more than it was originally planned.

Reason

統合失調症におけるグリア仮説、特にミクログリア仮説を検証するために、モデル動物を用いた実験に加えて、ヒト血液由来直接誘導ミクログリア様細胞（iMG細胞）を用いたトランスレーショナル研究を実施している。Cuprizone投与モデルマウスにおいて、海馬におけるミクログリア活性化を認め、特定の薬剤が活性化制御することを見出しており、現在、論文投稿中である。

Research Output

• [Journal Article] Identification of the Hikikomori syndrome of social withdrawal: Psychosocial features and treatment preferences in four countries (2015)
  • Author(s): Teo AR, Fetters MD, Stufflebam S, Tateno M, Balhara YBS, Choi TY, Kanba S, Mathews CA, Kato TA
  • Journal Title: International Journal of Social Psychiatry Volume : 61(1) Pages : 64-72
• [Journal Article] Minocycline, a microglial inhibitor, diminishes terminal patients' delirium? (2014)
  • Author(s): Hayakawa K, Kato TA, Kojiro M, Monji A, Kanba S
  • Journal Title: American Journal of Geriatric Psychiatry Volume : 22(3) Pages : 314-315
• [Journal Article] ミクログリアと精神疾患 (2014)
  • Author(s): 加藤隆弘, 神庭重信
  • Journal Title: 生命の科学 Volume : 65(1) Pages : 37-42
• [Journal Article] 精神免疫学から観た身体疾患と精神疾患の生物学的共通基盤 (2014)
  • Author(s): 早川宏平, 加藤隆弘, 神庭重信
  • Journal Title: 精神科治療学 Volume : 29(2) Pages : 171-178
• [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
• [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] Anti-allergic mechanisms of Japanese herbal medicine, yokukansan on mast cells (2014)
  • Author(s): Yamamura K, Kato S, Kato TA, Mizoguchi Y, Monji A, Kanba S, Furue M, Takeuchi S
  • Journal Title: Journal of Dermatology Volume : 41(9) Pages : 808-814
• [Journal Article] Minocycline, a microglial inhibitor, reduces ‘honey trap’ risk in human economic exchange (2013)
  • Author(s): Watabe M, Kato TA, Tsuboi S, Ishikawa K, Hashiya K, Monji A, Utsumi H, Kanba S
  • Journal Title: Scientific Reports Volume : 3 Pages : 1685
• [Journal Article] Undergraduate medical students' attitudes toward psychiatry: an international cross-sectional survey between India and Japan (2013)
  • Author(s): Kato TA, Balhara YPS, Chawla JM, Tateno M, Kanba S
  • Journal Title: International Review of Psychiatry Volume : 25(4) Pages : 378-384
• [Journal Article] Aripiprazole and minocycline, but not haloperidol, suppress oligodendrocyte damage from interferon-γ-stimulated microglia in co-culture model (2013)
  • Author(s): Seki Y, Kato TA, Monji A, Mizoguchi Y, Horikawa H, Sato-Kasai M, Yoshiga D, Kanba S
  • Journal Title: Schizophrenia Research Volume : 151(1-3) Pages : 20-28
• [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: Frontiers in Human Neuroscience Volume : 7 Pages : 13
• [Journal Article] Missing and Possible Link between Neuroendocrine Factors (2013)
  • Author(s): Kato TA, Hayakawa K, Monji A, Kanba S
  • Journal Title: Neuropsychiatric Disorders and Microglia. Frontiers in Integrative Neuroscience Volume : 7 Pages : 53
• [Journal Article] Neuron-glia interaction as a possible glue to translate the mind-brain gap: A novel multi-dimensional approach toward psychology and psychiatry (2013)
  • Author(s): Kato TA, Watabe M, Kanba S
  • Journal Title: Frontiers in Psychiatry (Frontiers in Neuropsychiatric Imaging and Stimulation) Volume : 4 Pages : 139
• [Journal Article] Neuroinflammation in schizophrenia especially focused on the role of microglia (2013)
  • Author(s): Monji A, Kato TA, Mizoguchi Y, Horikawa H, Seki Y, Kasai M, Yamauchi Y, Yamada S, Kanba S
  • Journal Title: Progress in Neuro-Psychopharmacology & Biological Psychiatry Volume : 42 Pages : 115-121
• [Journal Article] A case of FTD with catatonia-like signs that temporarily resolved with zolpidem (2013)
  • Author(s): Isomura S, Monji A, Sasaki K, Baba S, Onitsuka T, Ohara T, Mizoguchi Y, Kato TA, Horikawa H, Seki Y, Kanba S
  • Journal Title: Neurology: Clinical Practice Volume : 3 Pages : 354-357
• [Presentation] Psychosocial stress and microglia-translational research focusing on human microglia (2014)
  • Author(s): Kato TA, Ohgidani M, Kanba S
  • Organizer: 第24回日本臨床精神神経薬理学会・第44回日本神経精神薬理学会 合同年会
  • Place of Presentation: 名古屋国際会議場, 名古屋
  • Year and Date: 2014-11-22
• [Presentation] Translational psychiatric research focusing on microglia - Does microglial modulation prevent psychosis? (2014)
  • Author(s): Kato TA, Kanba S
  • Organizer: Symposium (Organized by Itokawa M), The 9th International Conference on Early Psychosis
  • Place of Presentation: Keio Plaza Hotel, Tokyo
  • Year and Date: 2014-11-17
• [Presentation] ストレスとミクログリアー齧歯類モデルの知見とヒト血液由来直接誘導ミクログリア様細胞作製技術の応用 (2014)
  • Author(s): 加藤隆弘, 扇谷昌宏, 神庭重信
  • Organizer: 日本ストレス学会学術総会・第30回記念大会
  • Place of Presentation: 日本大学文理学部百年記念館, 東京
  • Year and Date: 2014-11-07
• [Presentation] Two translational research methods focusing on human microglia (induced microglia-like (iMG) cells / minocycline). DFG-JSPS SYMPOSIUM “SHARED PATHWAYS IN CNS DISORDERS" (2014)
  • Author(s): Kato TA, Ohgidani M, Watabe M, Kanba S
  • Organizer: DFG-JSPS SYMPOSIUM “SHARED PATHWAYS IN CNS DISORDERS"
  • Place of Presentation: Ludwig-Maximilians-University (LMU), Munich, Germany
  • Year and Date: 2014-06-30
• [Presentation] Antipsychotics and minocycline as a possible modulator of microglial inflammatory/oxidative stress response in schizophrenia
  • Author(s): Ohgidani M, Kato TA, Kanba S
  • Organizer: 4th European Conference on Schizophrenia Research
  • Place of Presentation: Berlin, Germany
• [Presentation] A single minocycline administration suppresses methamphetamine-induced behavioral sensitization in mice
  • Author(s): Kato TA, Yamato M, Shiba T, Mine T, Seki Y, Ohgidani M, Sagata N, Yamauchi Y, Mizoguchi Y, Yamada K, Monji A, Kanba S
  • Organizer: The 43th Society for Neuroscience Annual Meeting
  • Place of Presentation: San Diego, USA
• [Patent(Industrial Property Rights/JSPS)] Method of producing microglial cells
  • Inventor(s): 加藤隆弘, 扇谷昌宏, 神庭重信
  • Industrial Property Rights Holder: 九州大学
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: P13-0218
  • Filing Date: 2014-01-09
  • Application Year: 2014
• [Patent(Industrial Property Rights/JSPS)] Method of producing microglial cells.
  • Inventor(s): Kato TA, Ohgidani M, Kanba S
  • Industrial Property Rights Holder: Kato TA, Ohgidani M, Kanba S
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: G1301WO-PCT
  • Filing Date: 2015-01-09
  • Application Year: 2015