Elucidation of epigenome regulation mechanism by fatty acid binding protein
| Project/Area Number |
19K05899
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 38050:Food sciences-related
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| Research Institution | Tohoku Medical and Pharmaceutical University |
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Principal Investigator |
yamamoto yui 東北医科薬科大学, 医学部, 助教 (80635087)
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| Co-Investigator(Kenkyū-buntansha) |
大和田 祐二 東北大学, 医学系研究科, 教授 (20292211)
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2020: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
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| Keywords | FABP / FABP3 / 多価不飽和脂肪酸 / 抑制性介在神経 / 抑制性介在ニューロン / パルブアルブミン / GAD67 / GABA / ペリニューロナルネット / エピゲノム |
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| Outline of Research at the Start |
発育期（胎児期から乳幼児期）の低栄養暴露により、エピゲノム変化（DNAメチル化やヒストン修飾）が招来される。この変化は成長後も維持され、発達障害などの様々な疾患への感受性に影響を与える。この時期のエピゲノム変化は、一生を通じて持続し、次の世代へも影響を及ぼし得る。多価不飽和脂肪酸の過不足がエピゲノム変化の一因と考えられているが、その分子機構は不明である。本研究の目的は、細胞内脂肪酸輸送体の脂肪酸結合タンパク質（FABP）によって制御される神経細胞の脂質恒常性維持が、生涯を通じたエピゲノム制御にどのような意義を持つのか検証することである。
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| Outline of Final Research Achievements |
It has been suggested that lipid homeostasis changes in developmental brain are associated with abnormal neuroplasticity after growth. In this study, we examined the relationship between abnormal lipid metabolism and changes in neuroplasticity in inhibitory interneurons and astrocytes that are particularly vulnerable to environmental changes during development.
We mainly revealed that fatty acid binding protein (FABP) in the cortical inhibitory interneurons is involved in the expression of cognitive and emotional behaviors through regulation of neurite outgrowth, and that FABP in astrocyte is important in the control of lipid metabolism and it is also involved in the neuronal plasticity control through epigenetic regulation of genetic information.
These results are expected to contribute to the research and development of mental illness and health medicine.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究により、発達期脳内脂質環境の変化が、新たなタンパク質相互作用を生み出し、エピゲノム修飾に影響を及ぼすことが示唆される。今後さらに詳細な解析を加えることで、FABPが関与する発達障害の病態解明、治療創薬の開発に大きく貢献できると考える。
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Report
(4 results)
Research Products
(21 results)
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[Journal Article] FABP7 Regulates Acetyl-CoA Metabolism Through the Interaction with ACLY in the Nucleus of Astrocytes2020
Author(s)
Kagawa Y, Umaru BA, Shima H, Ito R, Zama R, Islam A, Kanno S, Yasui A, Sato S, Jozaki K, Shil SK, Miyazaki H, Kobayashi S, Yamamoto Y, Kogo H, Shimamoto-Mitsuyama C, Sugawara A, Sugino N, Kanamori M, Tominaga T, Yoshikawa T, Fukunaga K, Igarashi K, Owada Y
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Journal Title
Molecular Neurobiology
Volume: 57
Issue: 12
Pages: 4891-4910
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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