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Translational research of psychiatric disorders focusing on neuron-glia interaction using regenerative medicine techniques

Research Project

Project/Area Number 26713039
Research Category

Grant-in-Aid for Young Scientists (A)

Allocation TypePartial Multi-year Fund
Research Field Psychiatric science
Research InstitutionKyushu University

Principal Investigator

Kato Takahiro  九州大学, 大学病院, 講師 (70546465)

Project Period (FY) 2014-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥23,530,000 (Direct Cost: ¥18,100,000、Indirect Cost: ¥5,430,000)
Fiscal Year 2017: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
Fiscal Year 2016: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
Fiscal Year 2015: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2014: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Keywordsミクログリア / 精神疾患 / 直接誘導ミクログリア様細胞 / 直接誘導ニューロン / 統合失調症 / うつ病 / 炎症仮説 / 再生医学 / iPS細胞 / iN細胞 / iMG細胞 / 橋渡し研究 / 双極性障害 / 気分障害 / トランスレーショナル研究 / 血液由来直接誘導ミクログリア様細胞 / 誘導ニューロン / 誘導ミクログリア
Outline of Final Research Achievements

We have originally developed a novel technique to induce microglia-like (iMG) cells directly from human peripheral blood (monocytes) by applying only two cytokines IL-34 and GM-CSF within two weeks without any gene modifications. Compared to the iPS cells, our iMG technique is simpler and has advantages of time and cost management. We have revealed abnormalities in cellular responses of iMG cells derived from patients with (1) Nasu-Hakola disease which is a known primary microglia disease. (2) bipolar disorder, and (3) fibromyalgia.
Direct conversion technique to produce induced-neuronal (iN) cells from human fibroblasts within 2 weeks is expected to discover unknown neuronal phenotypes of neuropsychiatric disorders. We have developed early-stage iN cells within a week. We have revealed unique gene expression profiles in iN cells and early-stage iN cells from patients with neurofibromatosis type 1 (NF1).

Report

(5 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Annual Research Report
  • 2015 Annual Research Report
  • 2014 Annual Research Report
  • Research Products

    (42 results)

All 2018 2017 2016 2015 2014 Other

All Int'l Joint Research (1 results) Journal Article (23 results) (of which Int'l Joint Research: 5 results,  Peer Reviewed: 19 results,  Open Access: 12 results,  Acknowledgement Compliant: 9 results) Presentation (11 results) (of which Int'l Joint Research: 3 results,  Invited: 1 results) Book (5 results) Patent(Industrial Property Rights) (2 results) (of which Overseas: 2 results)

  • [Int'l Joint Research] Johns Hopkins University/Oregon Health & Science University(米国)

    • Related Report
      2017 Annual Research Report
  • [Journal Article] Tryptophan-kynurenine and lipid related metabolites as blood biomarkers for first-episode drug-naive patients with major depressive disorder: an exploratory pilot case-control study.2018

    • Author(s)
      Kuwano N, Kato TA, Setoyama D, Sato-Kasai M, Shimokawa N, Hayakawa K, Ohgidani M, Sagata N, Kubo H, Kishimoto J, Kang D, Kanba S
    • Journal Title

      Journal of Affective Disorders

      Volume: 231 Pages: 74-82

    • DOI

      10.1016/j.jad.2018.01.014

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Blood biomarkers of Hikikomori, a severe social withdrawal syndrome.2018

    • Author(s)
      Hayakawa K, Kato TA*, Watabe M, Teo AR, Horikawa H, Shimokawa N, Sato-Kasai M, Kubo H, Ohgidani M, Sagata N, Toda H, Tateno M, Shinfuku N, Kishimoto J, Kanba S
    • Journal Title

      Scientific Reports

      Volume: 8 Issue: 1 Pages: 2884-2884

    • DOI

      10.1038/s41598-018-21260-w

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Hikikomori: experience in Japan and international relevance.2018

    • Author(s)
      Kato TA*, Kanba S, Teo AR
    • Journal Title

      World Psychiatry

      Volume: 17(1) Issue: 1 Pages: 105-106

    • DOI

      10.1002/wps.20497

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] 精神疾患における炎症性サイトカインを介したミクログリア病態治療仮説2018

    • Author(s)
      加藤隆弘, 神庭重信
    • Journal Title

      日本医事新報

      Volume: 4895 Pages: 36-42

    • Related Report
      2017 Annual Research Report
  • [Journal Article] 末梢血バイオマーカーを用いた精神医学評価システムの構築 ;現代のうつ病診断・評価における困難の打開に向けて 特集 Research Domain Criteria(RDoC)プロジェクトの目指す新たな精神医学診断・評価システム2018

    • Author(s)
      加藤隆弘
    • Journal Title

      精神医学

      Volume: 60(1) Pages: 51-62

    • NAID

      40021442575

    • Related Report
      2017 Annual Research Report
  • [Journal Article] Donepezil suppresses intracellular Ca2+ mobilization through the PI3K pathway in rodent microglia2017

    • Author(s)
      Haraguchi Yoshinori、Mizoguchi Yoshito、Ohgidani Masahiro、Imamura Yoshiomi、Murakawa-Hirachi Toru、Nabeta Hiromi、Tateishi Hiroshi、Kato Takahiro A.、Monji Akira
    • Journal Title

      J Neuroinflammation.

      Volume: 14 Issue: 1 Pages: 258-258

    • DOI

      10.1186/s12974-017-1033-0

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Modern-Type Depression as an "Adjustment" Disorder in Japan: The Intersection of Collectivistic Society Encountering an Individualistic Performance-Based System.2017

    • Author(s)
      Kato TA, Kanba S
    • Journal Title

      American Journal of Psychiatry

      Volume: 174(11) Issue: 11 Pages: 1051-1053

    • DOI

      10.1176/appi.ajp.2017.17010059

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Fibromyalgia and microglial TNF-α: Translational research using human blood induced microglia-like cells2017

    • Author(s)
      Ohgidani Masahiro、Kato Takahiro A.、Hosoi Masako、Tsuda Makoto、Hayakawa Kohei、Hayaki Chie、Iwaki Rie、Sagata Noriaki、Hashimoto Ryota、Inoue Kazuhide、Sudo Nobuyuki、Kanba Shigenobu
    • Journal Title

      Scientific Reports

      Volume: 7 Issue: 1 Pages: 1-6

    • DOI

      10.1038/s41598-017-11506-4

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Dysregulated gene expressions of MEX3D, FOS and BCL2 in human induced-neuronal (iN) cells from NF1 patients: a pilot study2017

    • Author(s)
      Sagata N, Kato TA, Kano SI, Ohgidani M, Shimokawa N, Sato-Kasai M, Hayakawa K, Kuwano N, Wilson AM, Ishizuka K, Kato S, Nakahara T, Nakahara-Kido M, Setoyama D, Sakai Y, Ohga S, Furue M, Sawa A, Kanba S.
    • Journal Title

      Sci Rep.

      Volume: 7 Issue: 1 Pages: 13905-13905

    • DOI

      10.1038/s41598-017-14440-7

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Early-onset epileptic encephalopathy and severe developmental delay in an association with de novo double mutations in NF1 and MAGEL22017

    • Author(s)
      Akamine S、Sagata N、Sakai Y、Kato TA.、Nakahara T、Matsushita Y、Togao O、Hiwatashi A、Sanefuji M、Ishizaki Y、Torisu H、Saitsu H、Matsumoto N、Hara T、Sawa A、Kano S、Furue M、Kanba S、Shaw CA.、Ohga S
    • Journal Title

      Epilepsia Open

      Volume: 3 Issue: 1 Pages: 81-85

    • DOI

      10.1002/epi4.12085

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] 精神疾患のミクログリア病態治療仮説 橋渡し研究による仮説解明をめざして2017

    • Author(s)
      加藤隆弘, 扇谷昌宏, 神庭重信
    • Journal Title

      BRAIN and NERVE

      Volume: 69(9) Pages: 1007-1015

    • Related Report
      2017 Annual Research Report
  • [Journal Article] 血液メタボローム解析による、うつ重症度・自殺念慮のバイオマーカー開発2017

    • Author(s)
      加藤隆弘, 瀬戸山大樹, 橋本亮太, 功刀浩, 服部功太郎, 康東天, 神庭重信
    • Journal Title

      分子精神医学

      Volume: 17(3) Pages: 199-205

    • Related Report
      2017 Annual Research Report
  • [Journal Article] Microglial CD206 gene has potential as a state marker of bipolar disorder2017

    • Author(s)
      1.Ohgidani M, Kato TA, Haraguchi Y, Matsushima T, Mizoguchi Y, Murakawa-Hirachi T, Sagata N, Monji A, Kanba S.
    • Journal Title

      Frontiers in Immunology

      Volume: 7 Pages: 676-676

    • DOI

      10.3389/fimmu.2016.00676

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Aripiprazole inhibits polyI:C-induced microglial activation possibly via TRPM72016

    • Author(s)
      Sato-Kasai M, Kato TA, Ohgidani M, Mizoguchi Y, Sagata N, Inamine S, Horikawa H, Hayakawa K, Shimokawa N, Kyuragi S, Seki Y, Monji A, Kanba S.
    • Journal Title

      Schizophrenia Research

      Volume: 178(1-3) Issue: 1-3 Pages: 35-43

    • DOI

      10.1016/j.schres.2016.08.022

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Plasma metabolites predict severity of depression and suicidal ideation in psychiatric patients-a multicenter pilot analysis2016

    • Author(s)
      Setoyama D, Kato TA, Hashimoto R, Kunugi H, Hattori K, Hayakawa K, Sato-Kasai M, Shimokawa N, Kaneko S, Yoshida S, Goto YI, Yasuda Y, Yamamori H, Ohgidani M, Sagata N, Miura D, Kang D, Kanba S
    • Journal Title

      PLoS ONE

      Volume: 11 Issue: 12 Pages: e0165267-e0165267

    • DOI

      10.1371/journal.pone.0165267

    • URL

      https://localhost/en/publications/71e3ad6d-9fc5-40c4-9d4e-eb15a2d63e45

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] TNF-α from hippocampal microglia directly induces working memory deficits by acute stress in mice.2016

    • Author(s)
      Ohgidani M, Kato TA*, Sagata N, Hayakawa K, Shimokawa N, Sato-Kasai M, Kanba S
    • Journal Title

      Brain, Behavior, and Immunity

      Volume: in press Pages: 17-24

    • DOI

      10.1016/j.bbi.2015.08.022

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Directly induced glial/neuronal cells from human peripheral tissues: A novel translational research for neuropsychiatric disorders2016

    • Author(s)
      Kato TA, Ohgidani M, Sagata N, Kanba S
    • Journal Title

      Advances in Neuroimmune Biology

      Volume: 6(2) Issue: 2 Pages: 95-105

    • DOI

      10.3233/nib-160109

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] NF-α from hippocampal microglia directly induces working memory deficits by acute stress in mice.2016

    • Author(s)
      Ohgidani M, Kato TA*, Sagata N, Hayakawa K, Shimokawa N, Sato-Kasai M, Kanba S
    • Journal Title

      Brain, Behavior, and Immunity

      Volume: in press

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Introducing directly induced microglia-like (iMG) cells from fresh human monocytes: A novel translational research tool for psychiatric disorders.2015

    • Author(s)
      Ohgidani M, Kato TA*, Kanba S
    • Journal Title

      Frontiers in Cellular Neuroscience

      Volume: 9 Pages: 184-184

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Identification of the hikikomori syndrome of social withdrawal: Psychosocial features and treatment preferences in four countries2015

    • Author(s)
      Alan R. Teo, Michael D. Fetters, Kyle Stufflebam, Masaru Tateno, Yatan Balhara, TaeYoung Lee, Shigenobu Kanba, Carol Mathews, Takahiro A. Kato
    • Journal Title

      International Journal of Social Psychiatry

      Volume: 61 Issue: 1 Pages: 64-72

    • DOI

      10.1177/0020764014535758

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Relationship between Trusting Behaviors and Psychometrics Associated with Social Network and Depression among Young Generation: A Pilot Study2015

    • Author(s)
      Motoki Watabe, Takahiro A. kato, Alan R. Teo, Hideki Horikawa, Masaru Tateno, Kohei Hayakawa, Norihiro Shimokawa, Shigenobu Kanba
    • Journal Title

      PLoS One

      Volume: 10 Issue: 4 Pages: e0120183-e0120183

    • DOI

      10.1371/journal.pone.0120183

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [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 Issue: 1 Pages: 4957-4957

    • DOI

      10.1038/srep04957

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [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

    • DOI

      10.3389/fncel.2014.00370

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] Do human plasma metabolites predict severity of depression and suicidal ideation?. Symposium “Biomarker research for pathophysiology and treatment effect of affective disorders”2017

    • Author(s)
      Kato TA, Sanba S
    • Organizer
      5th Congress of Asian College of Neuropsychopharmacology
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] うつ病を考える biology、psychology、psychopathologyから 脳内免疫細胞ミクログリアに焦点づけた気分障害研究:「死の欲動」の起源はミクログリアか?2017

    • Author(s)
      加藤隆弘, 神庭重信
    • Organizer
      第14回日本うつ病学会総会・第17回日本認知療法・認知行動療法学会
    • Related Report
      2017 Annual Research Report
  • [Presentation] ミクログリア仮説に鑑みた気分障害の血液バイオマーカー研究. シンポジウム「うつ病における炎症・酸化ストレスの役割と創薬への発展性」2017

    • Author(s)
      加藤隆弘, 扇谷昌宏, 瀬戸山大樹, 康 東天, 神庭重信
    • Organizer
      第39回 日本生物学的精神医学会・第47回 日本神経精神薬理学会
    • Related Report
      2017 Annual Research Report
  • [Presentation] ミクログリア仮説に鑑みた気分障害の血液バイオマーカー研究. シンポジウム「情動・脳高次機能解明の手続きとしてのメタボローム解析」2017

    • Author(s)
      加藤隆弘, 扇谷昌宏, 瀬戸山大樹, 康 東天, 神庭重信
    • Organizer
      第39回 日本生物学的精神医学会・第47回 日本神経精神薬理学会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Translational Research Using Human Blood Directly Induced Microglia-Like (iMG) cells; over Gene Expression and Production of TNF-α after ATP Stimulation in iMG Cells from Patients with Fibromyalgia.2017

    • Author(s)
      Kato TA, Ohgidani M, Hosoi M, Kanba S
    • Organizer
      ACNP 56th Annual Meeting
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 精神科臨床での重要課題を如何にして生物学的研究で解決するか?-ヒト末梢血由来直接誘導ミクログリア様細胞を用いた精神疾患トランスレーショナル研究-2016

    • Author(s)
      加藤 隆弘
    • Organizer
      脳科学と精神疾患―分子・細胞から精神疾患を読み解く―
    • Place of Presentation
      COEX, ソウル市, 韓国
    • Year and Date
      2016-07-03
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Psychosocial stress and microglia-translational research focusing on human microglia. 国際シンポジウム「ストレスによる神経炎症と神経疾患」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
    • Related Report
      2014 Annual Research Report
  • [Presentation] Possible biological and psychosocial risk factors of hikikomori among university students.2014

    • Author(s)
      Kato TA
    • Organizer
      Congress of Korean NeuroPsychiatric Association (KNPA)
    • Place of Presentation
      Jeju, South Korea
    • Year and Date
      2014-10-24
    • Related Report
      2014 Annual Research Report
  • [Presentation] 精神疾患患者のミクログリア活性化特性と精神病理現象との相関を解明するためのトランスレーショナル研究.2014

    • Author(s)
      加藤隆弘
    • Organizer
      第36回日本生物学的精神医学会 第57回日本神経化学会大会 合同年会
    • Place of Presentation
      奈良県新公会堂, 奈良
    • Year and Date
      2014-09-29
    • Related Report
      2014 Annual Research Report
  • [Presentation] Translational research focusing on risk of social isolation: Biological and psychological aspects among university students.2014

    • Author(s)
      Kato TA, Watabe M, Teo AR, Ohgidani M, Sagata A, Kubo H, Hayakawa K, Tateno M, Shimokawa N, Kanba S
    • Organizer
      WPA World Congress 2014
    • Place of Presentation
      Madrid, Spain
    • Year and Date
      2014-09-17
    • Related Report
      2014 Annual Research Report
  • [Presentation] Two translational research methods focusing on human microglia (induced microglia-like (iMG) cells / minocycline).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
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Book] Modulating Microglial Activation As a Possible Therapeutic Target for Depression in Understanding Depression : Volume 1. Biomedical and Neurobiological Background2018

    • Author(s)
      Sato-Kasai M, Kato TA, Ohgidani M, Horikawa H, Mizoguchi Y, Monji A, Kanba S
    • Total Pages
      322
    • Publisher
      Springer Singapore
    • ISBN
      9789811065804
    • Related Report
      2017 Annual Research Report
  • [Book] New Delhi-India2016

    • Author(s)
      Srinivasan V, López-Muñoz F, De Berardis D, Álamo C, Kato TA (Editors)
    • Total Pages
      921
    • Publisher
      Spri nger
    • Related Report
      2016 Annual Research Report
  • [Book] New Delhi-India2016

    • Author(s)
      Ohgidani M, Kato TA, Mizoguchi M, Horikawa H, Monji A, Kanba S
    • Total Pages
      921
    • Publisher
      Spri nger
    • Related Report
      2016 Annual Research Report
  • [Book] The Intersection of Culture and Solitude: The Hikikomori Phenomenon in Japan (Chapter 25). pp445-460, A HANDBOOK OF SOLITUDE: PSYCHOLOGICAL PERSPECTIVES ON SOCIAL ISOLATION, SOCIAL WITHDRAWAL, AND BEING ALONE (Edited by Robert J. Coplan & Julie Bowker)2014

    • Author(s)
      Teo AR, Stufflebam K, Kato TA
    • Total Pages
      588
    • Publisher
      Wiley-Blackwell, New York
    • Related Report
      2014 Annual Research Report
  • [Book] Neurodevelopmental and neuropsychiatric disorders. Chapter 14, pp345-372 "Microglia in health and disease” (Edited by Tremblay MÈ, , Sierra A)2014

    • Author(s)
      Monji A, Maezawa I, Mizoguchi Y, Kato TA, Jin LW
    • Total Pages
      486
    • Publisher
      Springer, New York
    • Related Report
      2014 Annual Research Report
  • [Patent(Industrial Property Rights)] Human plasma metabolites predict severity of depression2015

    • Inventor(s)
      加藤隆弘, 瀬戸山大樹, 神庭重信, 他
    • Industrial Property Rights Holder
      加藤隆弘, 瀬戸山大樹, 神庭重信, 他
    • Industrial Property Rights Type
      特許
    • Filing Date
      2015-11-12
    • Related Report
      2015 Annual Research Report
    • Overseas
  • [Patent(Industrial Property Rights)] Method of producing microglial cells.2015

    • Inventor(s)
      Kato TA, Ohgidani M, Kanba S
    • Industrial Property Rights Holder
      Kyushu University
    • Industrial Property Rights Type
      特許
    • Filing Date
      2015-01-09
    • Related Report
      2014 Annual Research Report
    • Overseas

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Published: 2014-04-04   Modified: 2019-12-27  

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