2023 Fiscal Year Research-status Report
Exploring a novel molecular pathway that underlies cerebellar contribution to autism spectrum disorder
| Project/Area Number |
23K14826
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| Research Institution | Tokai University |
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Principal Investigator |
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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| Project Period (FY) |
2023-04-01 – 2025-03-31
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| Keywords | Neurotropic factors / cerebellum development |
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| Outline of Annual Research Achievements |
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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| Current Status of Research Progress |
Current Status of Research Progress
2: Research has progressed on the whole more than it was originally planned.
Reason
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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| Strategy for Future Research Activity |
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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| Causes of Carryover |
In the first fiscal year, I ordered the majority of needed items from the grant money. However, I sometimes use common materials in our lab purchased from my supervisor grant to save some amount of money to use it together with the second year grant because several expensive experiments are still needed. In the second fiscal year, I will use the majority of the money to generate several lines of genetically modified (GM) mice using in vivo genome editing to confirm the casuality between NDNF-its receptor and brain development. In addition, I need to prepare big number of GM mice to test the therapeutic potential of NDNF.
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