Molecular mechanisms of the remyelination in chronic phase of spinal cord injury

• Project/Area Number: 26282159
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Rehabilitation science/Welfare engineering
• Research Institution: National Rehabilitation Center for Persons with Disabilities
• Principal Investigator: OGATA TORU 国立障害者リハビリテーションセンター(研究所), 病院(併任研究所)障者健康増進・運動医科学支援センター, センター長 (00392192)
• Co-Investigator(Kenkyū-buntansha): 長尾 元史 国立障害者リハビリテーションセンター(研究所), 研究所 運動機能系障害研究部, 研究室長 (00359671) ; 杉森 道也 富山大学, 大学院医学薬学研究部(医学), 助教 (20464026)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥15,210,000 (Direct Cost: ¥11,700,000、Indirect Cost: ¥3,510,000); Fiscal Year 2016: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2015: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2014: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000)
• Keywords: 再髄鞘化 / エピジェネティクス / オリゴデンドロサイト / 前駆細胞 / カプリゾン / カプリゾンモデル

Outline of Final Research Achievements

Oligodendrocyte precursor cells (OPCs) act as a reservoir of new oligodendrocytes (OLs) in homeostatic and pathological conditions. OPCs are activated in response to spinal cord injury (SCI), to generate myelinating OLs. This OPC activation is the first step in the process of remyelination, and proper control of OPC activation is important for tissue repair following SCI. However, the molecular mechanisms underlying OPC activation, especially its epigenetic regulation, remain mostly unknown. In this study, we demonstrate that chromodomain helicase DNA binding protein 7 (Chd7), which is a member of the Chd family of chromatin remodelers and is a causative gene for human CHARGE syndrome, collaborates with Sox2 and regulates OPC activation following SCI.

Research Products

• [Journal Article] Oligodendrocyte Progenitor Cells Directly Utilize Lactate for Promoting Cell Cycling and Differentiation (2017)
  • Author(s): Ichihara Y, Doi T, Ryu Y, Nagao M, Sawada Y, Ogata T
  • Journal Title: J Cell Physiol Volume: 232 Issue: 5 Pages: 986-995
  • DOI: 10.1002/jcp.25690
  • Peer Reviewed / Open Access
• [Journal Article] The crucial role of Erk2 in demyelinating inflammation in the central nervous system. (2016)
  • Author(s): Okazaki R, Doi T, Hayakawa K, Morioka K, Imamura O, Takishima K, Hamanoue M, Sawada Y, Nagao M, Tanaka S, Ogata T
  • Journal Title: J Neuroinflammation Volume: 13 Issue: 1 Pages: 235-239
  • DOI: 10.1186/s12974-016-0690-8
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Elevated Levels of Phosphorylated Neurofilament Heavy Subunit in the Cerebrospinal Fluid of Patients with Lumbar Spinal Stenosis: Preliminary Findings. (2015)
  • Author(s): Ohya J, Takeshita K, et al.
  • Journal Title: Spine J Volume: 未定 Issue: 7 Pages: 1587-1592
  • DOI: 10.1016/j.spinee.2015.03.013
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Involvement of the Tyro3 receptor and its intracellular partner Fyn signaling in Schwann cell myelination. (2015)
  • Author(s): Yuki Miyamoto, Tomohiro Torii, Shuji Takada, Nobuhiko Ohno, Yurika Saitoh, Kazuaki Nakamura, Akihito Ito, Toru Ogata, Nobuo Terada, Akito Tanoue, and Junji Yamauchi
  • Journal Title: Mol. Biol. Cell Volume: 26 Issue: 19 Pages: 3489-3503
  • DOI: 10.1091/mbc.e14-05-1020
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Discovery of power-law growth in the self-renewal of heterogeneous glioma stem cell populations. (2015)
  • Author(s): Sugimori, M., Hayakawa, H., Boman, B.M., Fields, J.Z., Awaji, M., Kozano, H., Tamura, R., Yamamoto, S., Ogata, T., Yamada, M., Endo, S., Kurimoto, M. and Kuroda, S.
  • Journal Title: PLoS ONE Volume: 10 Issue: 8 Pages: e0135760-e0135760
  • DOI: 10.1371/journal.pone.0135760
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] 脊髄再生に関する取組みの現状と理学療法（リハビリテーション）の役割 (2014)
  • Author(s): 緒方徹
  • Organizer: 第11回神経理学療法学会
  • Place of Presentation: つくば国際会議場, 茨城
  • Year and Date: 2014-12-06
• [Presentation] 脊髄損傷後のコレステロール代謝阻害剤投与は髄鞘の再生を阻害する (2014)
  • Author(s): 緒方徹
  • Organizer: 第33回日本運動器移植・再生医学研究会
  • Place of Presentation: 第一ホテル両国, 東京
  • Year and Date: 2014-09-27