| Project/Area Number |
22KJ3080
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| Project/Area Number (Other) |
22J10152 (2022)
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| Research Category |
Grant-in-Aid for JSPS Fellows
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| Allocation Type | Multi-year Fund (2023)
Single-year Grants (2022) |
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| Section | 国内 |
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| Review Section |
Basic Section 46010:Neuroscience-general-related
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| Research Institution | Okinawa Institute of Science and Technology Graduate University |
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Principal Investigator |
Mi Yang 沖縄科学技術大学院大学, 科学技術研究科, 特別研究員(DC2)
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| Project Period (FY) |
2023-03-08 – 2024-03-31
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| Project Status |
Completed (Fiscal Year 2023)
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| Budget Amount *help |
¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2023: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2022: ¥900,000 (Direct Cost: ¥900,000)
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| Keywords | Neuroimmunity / Cerebellum / Neurodevelopment / Autism |
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| Outline of Research at the Start |
It is known that MIA due to infection during pregnancy is a key environmental factor in ASD by affecting fetal development. Some studies have confirmed that MIA is associated with cerebellar abnormalities (one of the most common sites of abnormality in ASD) in the offspring. In this study, I found that maternal ifnb defects fetal cerebellar development. The involvement of ifnb in MIA will be further investigate in this project. These analyses will provide new insights into the mechanisms of neurological disorders and may contribute to the development of new therapeutic strategies for ASD.
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| Outline of Annual Research Achievements |
Maternal immune activation (MIA) triggered by viral infection during pregnancy is known to be a risk factor for neurodevelopmental disorders (NDDs). Although cerebellar structural and functional differences are associated with NDDs, little is known about the effects of MIA on fetal cerebellar development and its underlying mechanisms. Here, I found that polyinosinic:polycytidylic acid (poly(I:C))-induced MIA causes motor alterations in the offspring in adulthood. Moreover, single-cell RNA sequencing and immunofluorescence analyses revealed that MIA impairs the migration and generation of glutamatergic cerebellar nuclei (CN) neurons expressing Lhx9 and Meis2 in cerebellar development. Importantly, administration of interferon (IFN)-β, a type-I IFN produced in MIA, also mimics these changes in cerebellar development. While seemingly contradictory, the loss of type-I IFN signaling by administration of a neutralizing antibody of the receptor also restricts neuronal migration in cerebellar development. Finally, administration of IFN-β to pregnant mice results in motor alteration in the offspring. These findings suggest that although baseline type-I IFN signaling is required for normal cerebellar development, the excessive production of IFN-β in response to MIA disrupts cerebellar development and leads to motor behavioral abnormalities in the offspring.
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