Analysis of ischemia-induced neuronal cell death

• Project/Area Number: 26860139
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: General anatomy (including histology/embryology)
• Research Institution: Juntendo University
• Principal Investigator: SUNABORI Takehiko 順天堂大学, 医学部, 助教 (00407115)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 低酸素 / 脳虚血 / 脳梗塞 / 神経細胞死 / Toll様受容体 / オートファジー / 炎症性サイトカイン / 海馬

Outline of Final Research Achievements

Toll like receptors are one of the main contributors that induce inflammation under tissue injury and infection. We have previously reported that not only the excessive inflammation induced by TLR2, but also autophagy induction could aggravate disease states after neonatal hypoxic/ischemic (H/I) brain injury. Herein, we showed that the activation of TLR2 could directly induce autophagy after H/I injury. In contrast, the autophagy-impairment also revealed suppression of proinflammatory cytokine. Taken together, these data suggest that the activation of the TLR2-signaling pathway and autophagy induction leads to neuronal cell death in a synergistic action after neonatal-H/I brain injury.

Research Products

• [Journal Article] Suppression of ischemia-induced hippocampal pyramidal neuron death by hyaluronan tetrasaccharide through inhibition of toll-like receptor 2 signaling pathway (2016)
  • Author(s): Takehiko Sunabori, Masato Koike, Akira Asari, Yoji Oonuki, Yasuo Uchiyama
  • Journal Title: American Journal of Pathology Volume: 印刷中
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Cathepsin D in pancreatic acinar cells is implicated in cathepsin B and L degradation, but not in autophagic activity. (2016)
  • Author(s): Mehanna, S, Suzuki, C., Shibata, M., Sunabori, T., Imanaka, T., Araki, K., Yamamura, K., Uchiyama, Y. and Ohmuraya, M.
  • Journal Title: Biochem. Biophys. Res. Commun. Volume: 469 Issue: 3 Pages: 405-411
  • DOI: 10.1016/j.bbrc.2015.12.002
  • Peer Reviewed
• [Presentation] オリゴデンドロサイト分化におけるｍTORC1活性化の意義 (2016)
  • Author(s): 砂堀 毅彦、名田 茂之、岡田 雅人、内山 安男、小池 正人
  • Organizer: 第121回日本解剖学会総会･全国学術集会
  • Place of Presentation: ビッグパレットふくしま
  • Year and Date: 2016-03-28
  • Invited
• [Presentation] Toll like receptors control neuronal cell death via regulating the activation and production of nitric oxide in microglia cells of cathepsin D-deficient mice (2015)
  • Author(s): 砂堀毅彦
  • Organizer: 第120回日本解剖学会
  • Place of Presentation: 神戸
  • Year and Date: 2015-03-21 – 2015-03-23
• [Presentation] オリゴデンドロサイト分化におけるmTORC1活性化の意義 (2015)
  • Author(s): 砂堀毅彦
  • Organizer: 第20回グリアクラブ
  • Place of Presentation: 函館
  • Year and Date: 2015-01-26 – 2015-01-28