Elucidation of mechanisms for destruction and fixation of glia-syncytium in demyelinating diseases by whole-genome sequencing and immunohistochemical analysis.
| Project/Area Number |
16H02657
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Neurology
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| Research Institution | Kyushu University |
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Principal Investigator |
Kira Jun-ichi 九州大学, 医学研究院, 教授 (40183305)
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| Co-Investigator(Kenkyū-buntansha) |
松下 拓也 九州大学, 大学病院, 講師 (00533001)
山口 浩雄 九州大学, 大学病院, 特任講師 (00701830)
山崎 亮 九州大学, 医学研究院, 准教授 (10467946)
山本 健 久留米大学, 医学部, 教授 (60274528)
篠田 紘司 九州大学, 医学研究院, 助教 (70747998)
真崎 勝久 九州大学, 医学研究院, 助教 (90612903)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥47,320,000 (Direct Cost: ¥36,400,000、Indirect Cost: ¥10,920,000)
Fiscal Year 2018: ¥13,650,000 (Direct Cost: ¥10,500,000、Indirect Cost: ¥3,150,000)
Fiscal Year 2017: ¥13,650,000 (Direct Cost: ¥10,500,000、Indirect Cost: ¥3,150,000)
Fiscal Year 2016: ¥20,020,000 (Direct Cost: ¥15,400,000、Indirect Cost: ¥4,620,000)
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| Keywords | 多発性硬化症 / GWAS / アストログリア / オリゴデンドログリア / コネキシン / ミクログリア / 視神経脊髄炎 / グリアシンシチウム / 免疫グリア細胞間相互作用 / T細胞 |
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| Outline of Final Research Achievements |
T cell receptor gene rearrangement analysis clarified preserved base sequence specifically in patients with multiple sclerosis (MS). Vδ1/Vδ2 ratio in peripheral blood γδT cells correlated with the severity of MS. In pathological study, GLUT5 positive microglia accumulated in acute demyelinating lesions of MS and neuromyelitis optica, suggesting that microglia induce disruption of energy transportation system and result in demyelination and axonal change.
When experimental autoimmune encephalomyelitis (EAE) was induced in astroglia-specific connexin (Cx) 43-ablated mice, the clinical symptoms of EAE were alleviated. On the other hand, EAE became worse in oligodendroglia-specific Cx47-ablated mice. These results strongly suggest that the activation status of microglia by functional modification of connexins is deeply involved in the pathogenesis of demyelinating diseases.
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| Academic Significance and Societal Importance of the Research Achievements |
中枢神経炎症性疾患においてグリア細胞と免疫細胞との相互作用による神経障害機序についてその関連に関わる分子を同定した。グリアシンシチウムは中枢神経系の神経細胞以外の細胞が形成するネットワークで、ギャップ結合による直接的な結合と、液性因子による間接的なつながりが考えられるが、そのどちらにもコネキシンが深く関与している。先天性コネキシン機能異常は様々な疾患をもたらすが、一方で後天的な中枢神経系疾患においてもその異常が病態に関わることが明らかとなった。コネキシンは重要な治療標的と考えられ、これまで治療困難であった数々の中枢神経変性・脱髄性疾患に対する新規治療法開発につながる。
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Report
(4 results)
Research Products
(36 results)
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[Presentation] Elucidation of pathophysiology of glial dysfunction in neurological/psychiatric disorders.2017
Author(s)
Jun-ichi Kira, Mitsuru Watanabe, Ryo Yamasaki, Takuya Matsushita, Hiroo Yamaguchi, Katsuhisa Masaki, Atsushi Fujita, Hayato Une, Mei Fang, Takayuki Fujii, Shintaro Hayashida, Ban-yu Saitoh, Wataru Shiraishi, Yinan Zhao, Ulfa Camelia Indiasari
Organizer
Glial disorders
Related Report
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[Presentation] Th1 cells inhibit the expression of connexins in astrocytes2016
Author(s)
Mitsuru Watanabe, Katsuhisa Masaki, Ryo Yamasaki, Jun Kawanokuchi, Hideyuki Takeuchi, Akio Suzumura, Jun-ichi Kira
Organizer
32ND CONGRESS OF THE EUROPEAN COMMITTEE FOR TREATMENT AND RESEARCH IN MULTIPLE SCLEROSIS
Place of Presentation
London, UK
Year and Date
2016-09-14
Related Report
Int'l Joint Research
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