Molecular mechanism of astrocytic damage via endocytosis of AQP4 in Neuromyelitis optica

• Project/Area Number: 26860656
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Neurology
• Research Institution: Tohoku University
• Principal Investigator: Nishiyama Shuhei 東北大学, 大学病院, 助教 (60636017)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 視神経脊髄炎 / アストロサイト / アクアポリン４ / 脳神経疾患 / 補体非依存性細胞傷害 / 補体依存性細胞傷害 / アクアポリン4抗体

Outline of Final Research Achievements

Purified NMO-IgG from Aquaporin 4(AQP4)-IgG positive 5 NMO patients cause AQP4 clusters in the cell membrane then endocytosis of AQP4 in primary cultured human astrocyte using confocal fluorescence microscope. At the same time, NMO-IgG cause regression of filopodia and lamellipodia of astrocyte, change its shapes. Astrocytic foot process are also regressed like beading which are seen in the NMO pathology.

Research Products

• [Presentation] The usefulness of cerebrospinal fluid lactic dehydrogenation enzyme in the evaluation of disease activity in inflammatory demyelinating diseases. (2015)
  • Author(s): Shuhei Nishiyama, Tatsuro Misu, Rina Takano, Yoshiki Takai, Toshiyuki Takahashi, Ichiro Nakashima, Kazuo Fujihara, Masashi Aoki
  • Organizer: ECTRIMS 2015
  • Place of Presentation: バルセロナ、スペイン
  • Year and Date: 2015-10-07
  • Int'l Joint Research
• [Presentation] 炎症性脱髄性疾患の疾患活動性評価における脳脊髄液中LDH値有用性の検討 (2015)
  • Author(s): 西山修平、三須建郎、高野里菜、高井良樹、高橋利幸、中島一郎、藤原一男、青木正志
  • Organizer: 日本神経学会学術集会
  • Place of Presentation: 朱鷺メッセ（新潟）
  • Year and Date: 2015-05-21
  • Int'l Joint Research
• [Presentation] 炎症性脱髄性疾患の診断・予後における髄液中GFAP濃度有用性の多施設横断的検討－サブ解析結果－ (2015)
  • Author(s): 西山修平、三須建郎、清水優子、横山和正、景山卓、高井良樹、高野里菜、高橋利幸、藤盛寿一、佐藤滋、中島一郎、糸山泰人、藤原一男、青木正志
  • Organizer: 日本神経学会学術集会
  • Place of Presentation: 福岡
  • Year and Date: 2015-05-21
• [Presentation] CSF markers in AQP4/MOG-IgG-positive NMOSD. (2014)
  • Author(s): Shuhei Nishiyama, Tatsuro Misu, Yuko Simizu, Kazumasa Yokoyama, Takashi Kageyama, Yoshiki Takai, Rina Takano, Toshiyuki Takahashi, Jun-ichi Fujimori, Sigeru Sato, Ichiro Nakashima, Yasuto Itoyama, Kazuo Fujihara, Masashi Aoki
  • Organizer: Charcot Foundation Annual Meeting
  • Place of Presentation: Baveno, Italy
  • Year and Date: 2014-11-26 – 2014-11-28
• [Presentation] AQP4 Immunology in NMOSD. (2014)
  • Author(s): Shuhei Nishiyama
  • Organizer: PACTRIMS 2014
  • Place of Presentation: 台北、台湾
  • Year and Date: 2014-11-06 – 2014-11-08
  • Invited
• [Presentation] Subanalysis of a multicentric cross-sectional study of CSF-GFAP in the diagnosis of inflammatory demyelinating diseases. (2014)
  • Author(s): S. Nishiyama, T. Misu, Y. Simizu, K. Yokoyama, T. Kageyama, Y. Takai, R. Takano, T. Takahashi, J. Fujimori, S. Sato, I. Nakashima, Y. Itoyama, K. Fujihara, M. Aoki
  • Organizer: MS Boston 2014
  • Place of Presentation: Boston, USA
  • Year and Date: 2014-09-14
• [Presentation] A multicenter, cross-sectional study of the usefulness of CSF-GFAP in the diagnosis and the prognosis of inflammatory CNS diseases. (2014)
  • Author(s): S. Nishiyama, T. Misu, Y. Simizu, K. Yokoyama, T. Kageyama, Y. Takai, R. Takano, T. Takahashi, J. Fujimori, S. Sato, I. Nakashima, Y. Itoyama, K. Fujihara, M. Aoki
  • Organizer: American Academy of Neurology
  • Place of Presentation: Philadelphia, USA
  • Year and Date: 2014-04-28
• [Remarks] 東北大学医学部神経内科 研究活動について
  • URL: http://www.neurol.med.tohoku.ac.jp/group.html