Mechanisms of reactive astrocyte's migration after spinal cord injury

• Project/Area Number: 22700342
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Neuroscience in general
• Research Institution: Keio University
• Principal Investigator: RENAULT-MIHARA Francois 慶應義塾大学, 医学部, 特任助教 (20570427)
• Project Period (FY): 2010 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2011: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2010: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
• Keywords: 発生 / 発達 / 再生神経科学 / 神経科学 / アストロサイト / 脊髄損傷 / 細胞移動

Research Abstract

Based on the observation that inhibition of Glycogen Synthase Kinase-3(GSK-3) stimulates the migration of astrocytes, the applicant was able to pharmacologically stimulate this beneficial effect of reactive astrocytes : the administration of a specific inhibitor of GSK-3 after contusive SCI resulted in an accelerated migration of reactive astrocytes that secluded inflammatory cells, reduced the size of the lesions scar, spared more myelinated fibers, and significantly enhanced functional improvement. These findings suggest that the pharmacological stimulation of reactive astrocyte migration holds promise as a new therapeutic strategy for the treatment of spinal cord injury.

Research Products

• [Journal Article] Beneficial compaction of spinal cord lesion by migrating astrocytes through Glycogen Synthase Kinase-3 inhibition (2011)
  • Author(s): Renault-Mihara F, Katoh H, Ikegami T, Iwanami A, Mukaino M, Tada H, Yasuda A, Nori S, Shibata S, Saito K, Matsushita M, Kaibuchi K, Okada S, Toyama Y, Nakamura M, and Okano H
  • Journal Title: EMBO Mol Med Volume: 3 Issue: 11 Pages: 682-96
  • DOI: 10.1002/emmm.201100179
  • Peer Reviewed
• [Journal Article] Sox10-Venus mice : a new tool for real-time labeling of neural crest lineage cells and oligodendrocytes (2010)
  • Author(s): Shibata S, Yasuda A, Renault-Mihara F, Suyama S, Katoh H, Inoue T, Inoue YU, Nagoshi N, Sato M, Nakamura M, Akazawa C, Okano H
  • Journal Title: Mol Brain Volume: 3(1) Pages: 31-31
  • Peer Reviewed
• [Journal Article] Anti-IL-6-receptor antibody promotes repair of spinal cord injury by inducing microglia-dominant inflammation (2010)
  • Author(s): Mukaino M, Nakamura M, Yamada O, Okada S, Morikawa S, Renault-Mihara F, Iwanami A, Ikegami T, Ohsugi Y, Tsuji O, Katoh H, Matsuzaki Y, Toyama Y, Liu M, Okano H
  • Journal Title: Exp Neurol Volume: 224(2) Pages: 403-14
  • Peer Reviewed
• [Journal Article] Sox10-Venus mice : a new tool for real-time labeling of neural crest lineage cells and oligodendrocytes. PMID : 21034515 (2010)
  • Author(s): Shibata S, Yasuda A, Renault-Mihara F, Suyama S, Katoh H, Inoue T, Inoue YU, Nagoshi N, Sato M, Nakamura M, Akazawa C, Okano H.
  • Journal Title: Molecular Brain. Volume: 3 Pages: 31-31
  • Peer Reviewed
• [Journal Article] Anti-IL-6-receptor antibody promotes repair of spinal cord injury by inducing microglia-dominant inflammation. PMID : 20478301 (2010)
  • Author(s): Mukaino M, Nakamura M, Yamada O, Okada S, Morikawa S, Renault-Mihara F, Iwanami A, Ikegami T, Ohsugi Y, Tsuji O, Katoh H, Matsuzaki Y, Toyama Y, Liu M, Okano H.
  • Journal Title: Experimental Neurology Volume: 224(2) Pages: 403-414
  • Peer Reviewed
• [Presentation] Beneficial compaction of spinal cord lesion by migrating astrocytes through Glycogen Synthase Kinase-3 inhibition (2011)
  • Author(s): F Renault-Mihara
  • Organizer: The 34th Annual Meeting of the Japan Neuroscience Society
  • Place of Presentation: Yokohama, Japan
  • Year and Date: 2011-09-15
• [Presentation] Oral Session : Beneficial compaction of spinal cord lesion by migrating a strocytes through Glycogen Synthase Kinase-3 inhibition (2011)
  • Author(s): F Renault-Mihara
  • Organizer: The 34^<th> Annual Meeting of the Japan Neuroscience Society
  • Place of Presentation: パシフィコ横浜(神奈川)
  • Year and Date: 2011-09-15
• [Presentation] Stimulation of reactive astrocytes' migration by specific inhibition of GSK-3 enhances locomotor recovery after spinal cord injury (2010)
  • Author(s): F Renault-Mihara, T.IKEGAMI, A.IWANAMI, H.KATOH, Y.TOYAMA, M.NAKAMURA, H.OKANO
  • Organizer: Society for Neuroscience 2010
  • Place of Presentation: Sun Diego, United States
  • Year and Date: 2010-11-14
• [Presentation] Stimulation of reactive astrocytes' migration by specific inhibition of GSK-3 enhances locomotor recovery after spinal cord injury (2010)
  • Author(s): F Renault-Mihara, T. Ikegami, A. Iwanami, H. Katoh, Y. Toyama, M. Nakamura, H. Okano
  • Organizer: 40th Annual Meeting of the Society for Neuroscience
  • Place of Presentation: San Diego, CA
• [Presentation] Stimulation of reactive astrocytes' migration by specific inhibition of GSK-3 enhances locomotor recovery after spinal cord injury (2010)
  • Author(s): F Renault-Mihara, T. Ikegami, A. Iwanami, H. Katoh, Y. Toyama, M. Nakamura, H. Okano
  • Organizer: 29th Naito Conference. GLIA WORLD-Dynamic Function of Glial Cells
  • Place of Presentation: Brain, Shonan, Japan
• [Presentation] Role and Mechanisms of reactive astrocytes' migration after spinal cord injury (2010)
  • Author(s): F Renault-Mihara, M. Mukaino, M. Shinozaki, M. Nakamura, Y. Toyama, H. Okano
  • Organizer: The 33rd Annual Meeting of the Japan Neuroscience Society
  • Place of Presentation: Kobe, Japan
• [Presentation] Stimulation of reactive astrocytes' migration by specific inhibition of GSK-3 enhances locomotor recovery after spinal cord injury (2010)
  • Author(s): F Renault-Mihara, T.IKEGAMI, A.IWANAMI, H.KATOH, Y.TOYAMA, M.NAKAMURA, H.OKANO
  • Organizer: 29th Naito Conference. GLIA WORLD-Dynamic Function of Glial Cells in the Brain
  • Place of Presentation: Zushi-City, Kanagawa, Japan
• [Presentation] Role and Mechanisms of reactive astrocytes' migration after spinal cord injury (2010)
  • Author(s): F Renault-Mihara, M.Mukaino, M.Shinozaki, M.Nakamura, Y.Toyama, H.Okano
  • Organizer: 日本神経科学学会年会Neuro2010
  • Place of Presentation: Kobe, Japan
• [Remarks]
  • URL: http://www.okano-lab.com/