Involvements of Reelin/Ephrin pathway for functional recovery of hemiplegic mice with neural cell transplant

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K09115
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56010:Neurosurgery-related
• Research Institution: St. Marianna University School of Medicine
• Principal Investigator: Suzuki Noboru 聖マリアンナ医科大学, 医学部, 教授 (40235982)
• Co-Investigator(Kenkyū-buntansha): 清水 潤 聖マリアンナ医科大学, 医学部, 教授 (30509964)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: リーリン / エフリン / 運動神経

Outline of Final Research Achievements

Neural stem cell transplantation was performed in a hemiplegic model, and role of the signaling pathway from reelin to ephrin in motor neuron differentiation was analyzed. Transplanted neurons produced reelin in the damaged cortex, where the transplanted neurons and neighboring host neurons induced Dab1 phosphorylation and Akt phosphorylation. In addition, CREB was activated and the phosphorylated CREB was migrated into nuclear. Transfection of wild-type Dab1 genes into neural stem cells derived from mice deficient in the Dab1 gene restored the co-expression of the synaptic scaffold protein Grip with complexes containing Ephrin Bs and Apoer-Dab1. Collectively, it was shown that intracellular signal transduction mediated by phosphorylated Dab1 is important for the reconstruction of neural networks in hemiplegic mice with neural transplantation.

Free Research Field

再生医学

Academic Significance and Societal Importance of the Research Achievements

脳卒中は身体機能障害や認知機能障害を引き起こし生活の質を低下させる。さらに介護の負担が増加し、経済的な損失が発生する。医療費の増加や労働力の減少ももたらす。我々は神経幹細胞が片麻痺マウスの運動機能を回復させる事を報告示してきた。本研究では神経細胞移植による運動神経回路再構築に関わる細胞分化・成熟による回復メカニズムを可用性分子レベルで解明した。リーリンをはじめとするこれら分子の役割と移植神経細胞と宿主神経組織の関連を明らかにしたことで、今後の神経再生治療法開発のための基盤となる知見を得た。