| 研究課題/領域番号 |
23K14826
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| 研究種目 |
若手研究
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| 配分区分 | 基金 |
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| 審査区分 |
小区分52030:精神神経科学関連
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| 研究機関 | 東海大学 |
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研究代表者 |
モハメド ダルウィシュ 東海大学, 医学部, 奨励研究員 (60938934)
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| 研究期間 (年度) |
2023-04-01 – 2025-03-31
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| 研究課題ステータス |
交付 (2023年度)
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| 配分額 *注記 |
4,420千円 (直接経費: 3,400千円、間接経費: 1,020千円)
2024年度: 1,950千円 (直接経費: 1,500千円、間接経費: 450千円)
2023年度: 2,470千円 (直接経費: 1,900千円、間接経費: 570千円)
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| キーワード | Neurotropic factors / cerebellum development / ASD / Cerebellum |
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| 研究開始時の研究の概要 |
The cerebellum has been involved in neurodevelopmental disorders such as autism spectrum disorders (ASD). However, the molecular mechanism underlying cerebellar development/function and its implication in ASD are not fully understood. We identified a novel neurotropic factor as a potential key molecule for cerebellar development and ASD. I will use mouse genetics, together with molecular, electrophysiological, and behavioral approaches to uncover a novel molecular pathway that underlies cerebellar development and its involvement in ASD pathophysiology.
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| 研究実績の概要 |
In the first fiscal year, I aimed to elucidate the receptor and signaling pathway of NDNF that work together to maintain proper brain development. To identify NDNF receptors and other binding partners, I performed co-immunoprecipitation-coupled mass spectrometry from HA-tagged NDNF mice brain and identified potential receptor and downstream signaling pathway for NDNF. Indeed, I confirmed this pathway using westernblot analysis. In addition, we discovered that the NDNF undergoes processing and cleavge into a potentially more potent form. Using in vitro experiments, this cleaved form showed superior effect compared to full-length NDNF.
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| 現在までの達成度 (区分) |
現在までの達成度 (区分)
2: おおむね順調に進展している
理由
I think that the progress during the first year was going well becasue we identified a novel signaling patwhay through NDNF that underlie brain development and function. In addition, we identified a potential active form of NDNF which could have a great therapeutic potential for treating neurodevelopmental disorders.
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| 今後の研究の推進方策 |
In the next year, I plan to investigate whether NDNF receptor is involved in cerebellum development and the pathophysiology of neurodevelopmental disorders, I will knockout the receptor in the cerebellum using virus-based in vivo genome editing and compare morphological and behavioral characteristics to those of Ndnf KO mice. Next, I will investigate whether activating NDNF signaling pathway restores cerebellum function in Ndnf KO mice to confirm causality between NDNF signaling pathways and brain development.
Besides, I aim to check the theraputic potential of NDNF in treating neurodevelopmental disorders. I will inject the cleaved and full length peptide into the cerebellum of neonatal Ndnf KO mice to investigate its therapeutic effect in preventing neurodevelopmental phenotypes.
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