Elucidation of roles of CRMP in neural circuit formation and regeneration and application for the treatment of spinal cord injury

• Project/Area Number: 26430043
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Nerve anatomy/Neuropathology
• Research Institution: Waseda University
• Principal Investigator: Ohshima Toshio 早稲田大学, 理工学術院, 教授 (20311334)
• Research Collaborator: NAGAI Jun
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 大脳皮質形成 / 樹状突起形成 / スパイン形成 / 神経再生 / 脊髄損傷 / キナーゼ / 神経発生 / 神経発達

Outline of Final Research Achievements

In present study, we analyzed the role of CRMP family proteins in brain development and neural regeneration by using mutant mice of CRMP genes. We reported orientation abnormality of basal dendrites of layer V neurons in cerebral cortex of CRMP4 KO mice and this phenotype became worse in CRMP 1/4 double KO mice (Takaya et al., 2017). We also reported the involvement of CRMP2 phosphorylation in dendritic spine formation (Jin et al., 2016). In neural regeneration, we found that suppression of CRMP2 phosphorylation promoted functional recovery of motor and sensory system after spinal cord injury (Nagai et al., 2016). We further showed that LKE, which modified the function of CRMP2, also promoted recovery of motor function after spinal cord injury (Kotaka et al., 2017). These results indicate the importance of CRMP family proteins in brain development and their involvements in neural regeneration.

Research Products

• [Journal Article] CRMP1 and CRMP4 are required for proper orientation of dendrites of cerebral pyramidal neurons in the developing mouse brain (2017)
  • Author(s): Takaya R, Nagai J, Piao W. Niisato E, Nakabayashi T, Yamazaki Y, Nakamura F, Yamashita N, Kolattukudy P. Goshima Y, Ohshima T
  • Journal Title: Brain Res Volume: 1655 Pages: 161-167
  • DOI: 10.1016/j.brainres.2016.11.003
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Lanthionine ketimine ester promotes locomotor recovery after spinal cord injury by reducing neuroinflammation and promoting axon growth (2017)
  • Author(s): Kotaka K, Nagai J, Hensley K, Ohshima T
  • Journal Title: BBRC Volume: 483 Issue: 1 Pages: 759-764
  • DOI: 10.1016/j.bbrc.2016.12.069
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Deletion of Crmp4 attenuates CSPG-induced inhibition of axonal growth and induces nociceptive recovery after spinal cord injury. (2016)
  • Author(s): Nagai J, Takaya R, Piao W, Goshima Y, Ohshima T.
  • Journal Title: Mol Cell Neurosci. Volume: 74 Pages: 42-48
  • DOI: 10.1016/j.mcn.2016.03.006
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Inhibition of CRMP2 phosphorylation repairs CNS by regulating neurotrophic and inhibitory responses. (2016)
  • Author(s): Nagai, J., Owada, K., Kitamura, Y., Goshima, Y., Ohshima, T.
  • Journal Title: Exp Neurol Volume: 277 Pages: 283-95
  • DOI: 10.1016/j.expneurol.2016.01.015
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Phosphorylation of CRMP2 by Cdk5 regulates dendritic spine development of cortical neuron in the mouse hippocampus (2016)
  • Author(s): Jin X, Sasamoto K, Nagai J, Yamazaki Y, Saito K, Goshima Y, Inoue T, Ohshima T.
  • Journal Title: Neural Plasticity Volume: - Pages: 1-7
  • DOI: 10.1155/2016/6790743
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Crmp4 deletion promotes recovery from spinal cord injury by neuroprotection and limited scar formation. (2015)
  • Author(s): Nagai, J., Kitamura, Y., Owada, K., Yamashita, N., Takei, K., Goshima, Y., Ohshima, T.
  • Journal Title: Sci. Rep. Volume: 5 Issue: 1 Pages: 8269-8269
  • DOI: 10.1038/srep08269
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] ランチオニンケチミンエステルによる神経炎症抑制と軸索伸長を介した脊髄損傷後の後肢運動機能の向上 (2016)
  • Author(s): 小高 謙, Kenneth Hensley, 大島 登志男
  • Organizer: 第39回日本分子生物学年会
  • Place of Presentation: 横は野
• [Presentation] CRMP2 dephosphorylation induces locomotor and sensory recovery after spinal cord injury (2015)
  • Author(s): Jun Nagai, Kazuki Owada, Yoshiteru Kitamura, Yoshio Goshima, Toshio Ohshima
  • Organizer: BMB2015
  • Place of Presentation: 神戸
  • Year and Date: 2015-12-10
• [Presentation] Dephosphorylation of CRMP2 enhances recovery after spinal cord injury (2015)
  • Author(s): Jun Nagai, Kazuki Owada, Yoshiteru Kitamura, Yoshio Goshima, Toshio Ohshima
  • Organizer: SfN Annual Meeting “Neuroscience 2015"
  • Place of Presentation: シカゴ・USA
  • Year and Date: 2015-10-20
  • Int'l Joint Research
• [Presentation] Genetic modifications of Crmp enhance axonal regrowth after spinal cord injury by reducing cytoskeletal destabilization and inflammatory responses (2014)
  • Author(s): J. Nagai, Y. Kitamura, K. Owasa, Y. Goshima, T. Ohshima
  • Organizer: SFN Neuroscience meeting 2014
  • Place of Presentation: Washijgton D.C., USA
  • Year and Date: 2014-11-18
• [Remarks] 脊髄損傷における新たな治療標的タンパク質を特定
  • URL: http://www.waseda.jp/top/news/21182