Elucidation of demyelination mechanism caused by astrocyte injury

• Project/Area Number: 15K19473
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Neurology
• Research Institution: Tohoku University
• Principal Investigator: Takai Yoshiki 東北大学, 大学病院, 医員 (40725743)
• 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: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: アストロサイト / 脱髄 / 視神経脊髄炎 / アクアポリン４ / 炎症性サイトカイン / 虚血性組織障害 / 多発性硬化症 / NMOモデルの確立 / 二次性脱髄機序の解明

Outline of Final Research Achievements

In this study, we focused on two types of different pathology related to astrocytes injury. One is the effect on the myelin sheath caused by destruction and disappearance of astrocytes which typified by neuromyelitis optica spectrum disorders (NMOSD), and the other is a tissue dammage caused by reactive astrocytes seen in multiple sclerosis and other inflammatory demyelinating disease. As a result, the influence of astrocyte destruction itself is limited. On the other hand, we found inflammatory cytokines produced by reactive astrocytes exhibit a special pattern of myelin sheath damage.

Research Products

• [Journal Article] Hypoxia-like tissue injury and glial response contribute to Balo concentric lesion development. (2016)
  • Author(s): Takai Y, Misu T, Nishiyama S, Ono H, Kuroda H, Nakashima I, Saito R, Kanamori M, Sonoda Y, Kumabe T, Mugikura S, Watanabe M, Aoki M, Fujihara K.
  • Journal Title: Neurology. Volume: Nov 8;87(19) Pages: 2000-2005
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] High avidity chimeric monoclonal antibodies against the extracellular domains of human aquaporin-4 competing with the neuromyelitis optica autoantibody, NMO-IgG. (2016)
  • Author(s): Miyazaki-Komine K, Takai Y, Huang P, Kusano-Arai O, Iwanari H, Misu T, Koda K, Mitomo K, Sakihama T, Toyama Y, Fujihara K, Hamakubo T, Yasui M, Abe Y.
  • Journal Title: Br J Pharmacol. Volume: 173 Pages: 103-103
  • DOI: 10.1111/bph.13340
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] The binding property of a monoclonal antibody against the extracellular domains of aquaporin-4 directs aquaporin-4 toward endocytosis. (2016)
  • Author(s): Huang P*, Takai Y*, Kusano AO, Ramadhanti J, Iwanari H, Miyauchi T, Sakihama T, YanHan J, Aoki M, Hamakubo T, Fujihara K, Yasui M, Abe Y. *authors with same contribution.
  • Journal Title: Biochemistry and Biophysics Reports Volume: 7 Pages: 77-83
  • DOI: 10.1016/j.bbrep.2016.05.017
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Severely exacerbated neuromyelitis optica rat model with extensive astrocytopathy by high affinity anti-aquaporin-4 monoclonal antibody. (2015)
  • Author(s): Kurosawa K, Misu T, Takai Y, Sato DK, Takahashi T, Abe Y, Iwanari H, Ogawa R, Nakashima I, Fujihara K, Hamakubo T, Yasui M, Aoki M.
  • Journal Title: Acta Neuropathol Commun. Volume: 4 Pages: 783-783
  • DOI: 10.1186/s40478-015-0259-2
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Presentation] Hypoxia-like tissue injury and glial response contribute to the development of Balo’s concentric demyelination (2016)
  • Author(s): Takai Y, Misu T, Nishiyama S, Ono H, Kuroda H, Nakashima I, Saito R, Kanamori M, Mugikura S, Watanabe M, Aoki M, Fujihara K.
  • Organizer: 9th Congress of the Pan-Asian Committee for Treatment and Research in Multiple Sclerosis
  • Place of Presentation: Bangkok, Thailand
  • Year and Date: 2016-10-27
  • Int'l Joint Research
• [Presentation] Balo病における同心円状脱髄病巣形成に対する虚血性組織障害とグリア細胞の関与 (2016)
  • Author(s): 高井 良樹、三須 建郎、西山 修平、黒田 宙、中島 一郎、渡辺 みか、齋藤 竜太、金森 政之、藤原 一男、青木 正志
  • Organizer: 第28回日本神経免疫学会学術集会
  • Place of Presentation: 長崎（長崎ブリックホール）
  • Year and Date: 2016-09-29
• [Presentation] Temporal changes of pathological features in NMO Spectrum Disorders with aquaporin4 antibody. (2016)
  • Author(s): Takai Y, Misu T, Nakashima I, Kuroda H, Takahashi T, Nishiyama S, Kaneko K, Akaishi T, Ogawa K, Fujihara K, Aoki M.
  • Organizer: 32nd Congress of the European Committee for Treatment and Research in Multiple Sclerosis
  • Place of Presentation: London, United Kingdom
  • Year and Date: 2016-09-14
  • Int'l Joint Research
• [Presentation] Chronological change is the main cause of histopathological diversity in neuromyelitis optica with anti-AQP4 antibody. (2016)
  • Author(s): Takai Y, Misu T, Nakashima I, Kuroda H, Takahashi T, Nishiyama S, Kaneko K, Akaishi T, Ogawa K, Fujihara K, Aoki M.
  • Organizer: 第57回日本神経学会学術大会
  • Place of Presentation: 神戸（神戸コンベンションセンター）
  • Year and Date: 2016-05-18
• [Presentation] Astrocyte injury and secondary demyelination induced by intracerebral injection of AQP4-IgG and complement in mouse brain. (2015)
  • Author(s): Yoshiki Takai, Yoichiro Abe, Tasturo Misu, Kazuhiro Kurosawa, Toshiyuki Takahashi, Hiroshi Kuroda, Ichiro Nakashima, Shuhei Nishiyama, Masato Yasui, Masashi Aoki, Kazuo Fujihara
  • Organizer: 8th Congress of the Pan-Asian committee for research and treatment of multiple sclerosis
  • Place of Presentation: ソウル（韓国）
  • Year and Date: 2015-11-19
  • Int'l Joint Research
• [Presentation] Astrocyte injury and secondary demyelination induced by intracerebral injection of AQP4-IgG and complement in mouse brain. (2015)
  • Author(s): Yoshiki Takai, Yoichiro Abe, Tasturo Misu, Kazuhiro Kurosawa, Toshiyuki Takahashi, Hiroshi Kuroda, Ichiro Nakashima, Shuhei Nishiyama, Masato Yasui, Masashi Aoki, Kazuo Fujihara
  • Organizer: 31st Congress of the european committee for treatment and research in multiplesclerosis
  • Place of Presentation: バルセロナ（スペイン）
  • Year and Date: 2015-10-07
  • Int'l Joint Research
• [Presentation] NMOモデルマウスにおけるアストロサイト障害に伴う二次性脱髄機序の解明 (2015)
  • Author(s): 高井 良樹、三須 建郎、黒沢 和大、高橋 利幸、中島 一郎、黒田 宙、西山 修平、藤原 一男、青木 正志
  • Organizer: 第27回日本神経免疫学会学術集会
  • Place of Presentation: 岐阜
  • Year and Date: 2015-09-15
• [Presentation] Astrocyte injury and secondary demyelination in intracranial injection mouse model of NMO. (2015)
  • Author(s): 高井 良樹、阿部 陽一郎、三須 建郎、ジュリア ラマダンティ、黒沢 和大、高橋 利幸、黒田 宙、中島 一郎、西山 修平、佐藤 ダグラス、安井 正人、藤原 一男、青木 正志
  • Organizer: 第56回神経学会学術大会
  • Place of Presentation: 新潟
  • Year and Date: 2015-05-20