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2017 Fiscal Year Annual Research Report

Elucidasion of functional contribution of glial dysturbances in pathomechanisms of demyelinating diseases and schizophrenia and development of new therapeutic options

Planned Research

Project AreaGlial assembly: a new regulatory machinery of brain function and disorders
Project/Area Number 25117012
Research InstitutionKyushu University

Principal Investigator

吉良 潤一  九州大学, 医学研究院, 教授 (40183305)

Co-Investigator(Kenkyū-buntansha) 松下 拓也  九州大学, 大学病院, 講師 (00533001)
山崎 亮  九州大学, 医学研究院, 准教授 (10467946)
Project Period (FY) 2013-06-28 – 2018-03-31
Keywordsグリア細胞 / コネキシン / EAE / GWAS
Outline of Annual Research Achievements

中枢神経系に存在する、神経細胞以外の細胞:グリア細胞は、広範囲な脳領域をカバーする「グリアアセンブリ」とよばれる一塊としての巨大ネットワークを形成している。私たちは、グリア細胞間でgap junctionを形成し細胞間コミュニケーションに極めて重要なconnexin(Cx)に着目し、同蛋白機能が多発性硬化症患者およびそのモデル動物でどのように関与しているかを解析した。また、他施設との共同研究で、精神疾患における同蛋白の機能解析を行った。1) 中枢性脱髄性疾患や統合失調症の多数例の剖検標本を用い(尾崎班と連携)、半定量的な分子免疫病理学的解析を継続している。2) 前年度までに作成したコネキシン欠損マウスを用い、実験的自己免疫性脳脊髄炎(EAE)の経過に及ぼす影響を検討した。アストログリア特異的Cx43ノックアウトマウスでは、灰白質のアストログリア特異的にCx43を欠損させるとEAEが軽症化した一方、白質のアストログリア特異的にCx43を欠損させても症状に変化を認めなかったことから、灰白質と白質とでは中枢炎症の環境下におけるアストログリアの挙動が異なることが強く示唆された。Cx30欠損マウスでは、やはりEAEは軽症化した。同マウスではミクログリアの神経保護的活性化が観察された。一方、オリゴデンドログリア特異的Cx47欠損マウスではEAEが重症化した。同マウスでは末梢血の炎症状態に変化なかったことから、中枢のグリア炎症が病態の変化に関与していると思われた。またこのマウスは世界初の二次進行性多発性硬化症のモデル動物として、今後の解析により新しい知見や治療法の開発が期待された。3) 脱髄性疾患や統合失調症のGWASおよび全ゲノムCNV解析し、疾患感受性に寄与する遺伝子を探索する(尾崎班と連携)。現在準備中。4) 間葉系細胞から脳移行性に優れたシュワン細胞を誘導し、EAEモデルラットへの移植実験を行う。現在は脳移行性シュワン細胞株樹立中。

Research Progress Status

29年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

29年度が最終年度であるため、記入しない。

  • Research Products

    (24 results)

All 2018 2017

All Journal Article (5 results) (of which Peer Reviewed: 5 results,  Open Access: 2 results) Presentation (19 results) (of which Int'l Joint Research: 5 results)

  • [Journal Article] Upregulation of Vesicular Glutamate Transporter 2 and STAT3 Activation in the Spinal Cord of Mice Receiving 3,3'-Iminodipropionitrile.2018

    • Author(s)
      Ohgomori T, Yamasaki R, Kira JI, Jinno S.
    • Journal Title

      Neurotox Res.

      Volume: 33 Pages: 768-780

    • DOI

      10.1007/s12640-017-9822-x.

    • Peer Reviewed
  • [Journal Article] Novel disease-modifying anti-rheumatic drug iguratimod suppresses chronic experimental autoimmune encephalomyelitis by down-regulating activation of macrophages/microglia through an NF-κB pathway.2018

    • Author(s)
      Li G, Yamasaki R, Fang M, Masaki K, Ochi H, Matsushita T, Kira JI.
    • Journal Title

      Sci Rep

      Volume: 31 Pages: 1933

    • DOI

      10.1038/s41598-018-20390-5.

    • Peer Reviewed / Open Access
  • [Journal Article] Differential activation of neuronal and glial STAT3 in the spinal cord of the SOD1(G93A) mouse model of amyotrophic lateral sclerosis.2017

    • Author(s)
      Ohgomori T, Yamasaki R, Takeuchi H, Kadomatsu K, Kira JI, Jinno S.
    • Journal Title

      Eur J Neurosci

      Volume: 46 Pages: 2001-2014

    • DOI

      10.1111/ejn.13650.

    • Peer Reviewed
  • [Journal Article] Differential involvement of vesicular and glial glutamate transporters around spinal α-motoneurons in the pathogenesis of SOD1(G93A) mouse model of amyotrophic lateral sclerosis.2017

    • Author(s)
      Ohgomori T, Yamasaki R, Takeuchi H, Kadomatsu K, Kira JI, Jinno S.
    • Journal Title

      Neuroscience

      Volume: 356 Pages: 114-124

    • DOI

      10.1016/j.neuroscience.2017.05.014.

    • Peer Reviewed
  • [Journal Article] Early strong intrathecal inflammation in cerebellar type multiple system atrophy by cerebrospinal fluid cytokine/chemokine profiles: a case control study.2017

    • Author(s)
      Yamasaki R, Yamaguchi H, Matsushita T, Fujii T, Hiwatashi A, Kira JI.
    • Journal Title

      J Neuroinflammation.

      Volume: 14 Pages: 89

    • DOI

      10.1186/s12974-017-0863-0.

    • Peer Reviewed / Open Access
  • [Presentation] Elucidation of pathophysiology of glial dysfunction in neurological/psychiatric disorders2017

    • Author(s)
      Kira J, Watanabe M, Yamasaki R, Matsushita T, Yamaguchi H, Masaki K, Fujita A, Une H, Fang M, Fujii T, Hayashida S, Saitoh BY, Shiraishi W, Tyou E, Camelia UI
    • Organizer
      Glial disorders
    • Int'l Joint Research
  • [Presentation] T-05-040C Astrocytic connexin 30 deletion leads to hypersensitivity in a MPTP mouse model of Parkinson’s disease2017

    • Author(s)
      Atsushi Fujita, MD,1 Hiroo Yamaguchi, MD, PhD,1 Ryo Yamasaki, MD, PhD,1 Yuta Matsuoka, PhD,2 Ken-ichi Yamada, PhD,2 Jun-ichi Kira, MD, PhD
    • Organizer
      Euroglia2017
  • [Presentation] "Astroglial and Oligodendroglial Connexins Differentially Influence Both Acute and Chronic Progressive Experimental Autoimmune Encephalomyelitis "2017

    • Author(s)
      Jun-ichi Kira, Ryo Yamasaki, Hayato Une, Mei Fang, Yinan Zhao, Guangrui Li, Hiroo Yamaguchi
    • Organizer
      The 4th MS summer college 2017
  • [Presentation] "Astroglial (Cx30, Cx43) and oligodendroglial (Cx47) connexins modulate acute and chronic experimental autoimmune encephalomyelitis (EAE) "2017

    • Author(s)
      "Ryo Yamasaki, Fang Mei, Hayato Une, Zhao Yinan, Hiroo Yamaguchi, Jun-ichi Kira "
    • Organizer
      The 4th MS summer college 2017
  • [Presentation] "Astroglial and Oligodendroglial Connexins Differentially Influence Both Acute and Chronic Progressive Experimental Autoimmune Encephalomyelitis "2017

    • Author(s)
      Jun-ichi Kira, Ryo Yamasaki, Hayato Une, Mei Fang, Yinan Zhao, Guangrui Li, Hiroo Yamaguchi
    • Organizer
      "International Gap Junction Conference Glasgow 2017 "
  • [Presentation] Neonatal allergen exposure induces autistic-like behavior via hippocampal synaptopathy in mice2017

    • Author(s)
      Ban-yu Saitoh, Daan Van Kruining, Claudia Thomsen, Ryo Yamasaki, Jun-ichi Kira
    • Organizer
      第60回日本神経化学会大会
  • [Presentation] "EARLY POSTNATAL ALLERGEN EXPOSURE INDUCES AUTISM-LIKE BEHAVIOR IN MALE MICE "2017

    • Author(s)
      Ban-yu Saitoh, Daan Van Kruining, Claudia Thomsen, Ryo Yamasaki, Jun-ichi Kira
    • Organizer
      XXIII World Congress of Neurology(WCN2017)
  • [Presentation] Experimental autoimmune encephalomyelitis is ameliorated in mice with gray matter astroglia-specific inducible connexin 43 knock-out2017

    • Author(s)
      "Hayato Une, Hiroo Yamaguchi, Yinan Zhao, Koji Shinoda, Katsuhisa Masaki, Magdalena Gotz, Ryo Yamasaki, and Jun-ichi Kira "
    • Organizer
      XXIII World Congress of Neurology(WCN2017)
  • [Presentation] Astroglial connexin 30 deletion leads to hypersensitivity in a MPTP mouse model of Parkinson’s disease2017

    • Author(s)
      Atsushi Fujita, 〇Hiroo Yamaguchi, Ryo Yamasaki, Yuta Matsuoka, Ken-ichi Yamada, Jun-ichi Kira
    • Organizer
      XXIII World Congress of Neurology(WCN2017)
  • [Presentation] Early strong intrathecal inflammation in cerebellar type multiple system atrophy (MSA-C) based on cerebrospinal fluid cytokine and chemokine profiles2017

    • Author(s)
      Ryo Yamasaki, Hiroo Yamaguchi, Takuya Matsushita, Takayuki Fujii, Akio Hiwatashi, Jun-ichi Kira
    • Organizer
      XXIII World Congress of Neurology(WCN2017)
  • [Presentation] "脱髄性疾患の神経炎症・神経変性におけるグリア細胞の役割 "2017

    • Author(s)
      吉良潤一
    • Organizer
      千里ライフサイエンスセミナー
  • [Presentation] "Astroglial and oligodendroglial connexins differentially modulate acute and chronic experimental autoimmune encephalomyelitis"2017

    • Author(s)
      Jun-ichi Kira, Ryo Yamasaki, Hayato Une, Mei Fang, Yinan Zhao, Guangrui Li, Kyoko Iinuma, Katsuhisa Masaki, Koji Shinoda, Hiroo Yamaguchi
    • Organizer
      the 142nd American Neurological Association Annual Meeting
    • Int'l Joint Research
  • [Presentation] Oligodendroglial Cx47 mediates myelin protective effects and plays a role in suppressing infiltration of inflammatory cells in autoimmune encephalomyelitis2017

    • Author(s)
      "Yinan Zhao, Ryo Yamasaki, Hiroo Yamaguchi, Hayato Une, Yiwen Cui, Jun-ichi Kira "
    • Organizer
      The 29th Annual Meeting of the Japanese Society Neuroimmunology
  • [Presentation] Connexin 30 欠損マウスにおける慢性進行期EAEの軽症化2017

    • Author(s)
      "山﨑 亮、方 梅、李 広瑞、藤田 篤史、宇根 隼人、山口 浩雄、吉良 潤一 "
    • Organizer
      第29回日本神経免疫学会学術集会
  • [Presentation] Astroglial connexin 30 deletion leads to hypersensitivity in a MPTP mouse model of Parkinson’s disease2017

    • Author(s)
      Atsushi Fujita, 〇Hiroo Yamaguchi, Ryo Yamasaki, Yuko Kobayakawa,Yuta Matsuoka,Ken-ichi Yamada,Jun-ichi Kira
    • Organizer
      Neuroscience 2017
  • [Presentation] "Oligodendroglia-specific Connexin 47 deletion induced relapse-remitting EAE model mice"2017

    • Author(s)
      "Ryo Yamasaki MD, PhD, Yinan Zhao, MD, Hiroo Yamaguchi MD, PhD, Jun-ichi Kira MD, PhD."
    • Organizer
      "10th PACTRIMS Ho Chi Minh City, Vietnam"
    • Int'l Joint Research
  • [Presentation] "Oligodendroglia-specific Connexin 47 deletion induced relapse-remitting EAE model mice"2017

    • Author(s)
      "Ryo Yamasaki MD, PhD, Yinan Zhao MD, Hiroo Yamaguchi MD, PhD, Jun-ichi Kira MD, PhD "
    • Organizer
      "10th PACTRIMS Ho Chi Minh City, Vietnam"
    • Int'l Joint Research
  • [Presentation] Underlying Mechanisms for How Environmental Allergens Modulate Neuroinflammation2017

    • Author(s)
      吉良潤一
    • Organizer
      "10th PACTRIMS Ho Chi Minh City, Vietnam"
    • Int'l Joint Research
  • [Presentation] Astroglial and oligodendroglial connexins differentially modulate acute and chronic experimental autoimmune encephalomyelitis2017

    • Author(s)
      Ryo Yamasaki, Mei Fang, Yinan Zhao, Hayato Une, Hiroo Yamaguchi, Jun-ichi Kira
    • Organizer
      The 22nd Annual Meeting of the Japan Glia

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Published: 2018-12-17  

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