| Project/Area Number |
20F20704
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| Research Category |
Grant-in-Aid for JSPS Fellows
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| Allocation Type | Single-year Grants |
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| Section | 外国 |
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| Review Section |
Basic Section 48020:Physiology-related
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| Research Institution | Kobe University |
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Principal Investigator |
内匠 透 (2020) 神戸大学, 医学研究科, 教授 (00222092)
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| Co-Investigator(Kenkyū-buntansha) |
BALASURIYA BALASURIYA 神戸大学, 医学研究科, 外国人特別研究員
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| Host Researcher |
内匠 透 (2021-2022) 神戸大学, 医学研究科, 教授 (00222092)
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| Foreign Research Fellow |
BALASURIYA BALASURIYA 神戸大学, 医学(系)研究科(研究院), 外国人特別研究員
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| Project Period (FY) |
2020-11-13 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 2022: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2021: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2020: ¥300,000 (Direct Cost: ¥300,000)
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| Keywords | autism / intestine |
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| Outline of Research at the Start |
Autism is a highly prevalent neurological disorder characterized by impaired social interactions and stereotyped or repetitive behaviours. Autism-associated GI symptoms frequently present from early childhood to adulthood and patients with autism are approximately four-fold more likely to be hospitalized with GI disorders. GI function is regulated by the intrinsic enteric nervous system (ENS). We characterize the GI phenotype in mouse models of autism in order to identify therapeutic targets to treat GI dysfunction.
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| Outline of Annual Research Achievements |
Chromosome 15q duplication Syndrome is a neurodevelopmental disorder. Approximately 80% of individuals with 15q duplications (15q dup) have gastrointestinal (GI) dysfunction, with frequent symptoms including gastroesophageal reflux and constipation. The duplicated region consists of genes encoding for GABA receptor A subunits and GABA is an important neurotransmitter in the Enteric Nervous System (ENS). The gut produces over 90% of the body's serotonin, and serotonin plays a vital role in the enteric neuronal circuitry that regulates gut motility. We investigated GI dysfunction and serotonin-mediated neurotransmission in the ENS. Both male and female adult 15q dup mice had delayed GI transit. We investigated colonic motility using a video imaging approach in which colonic contractions were assessed ex vivo using a video camera and in-house software. When 15q dup mice were treated with Bicuculine, colonic contractions were slower and traveled for a shorter distance. Since the 15q dup neurons were under a hypo-serotonin condition, the potential of Prucalopride to restore the delayed GI transit was investigated. Prucalopride reversed the delayed GI transit in 15q dup mice. The results suggest that enteric neurons in 15q dup mice are more susceptible to GABA receptor inhibition and targeting serotonin receptors is an effective way to treat GI dysfunction in 15q dup syndrome.
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| Research Progress Status |
令和4年度が最終年度であるため、記入しない。
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| Strategy for Future Research Activity |
令和4年度が最終年度であるため、記入しない。
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