| Project/Area Number |
18K17933
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 59040:Nutrition science and health science-related
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| Research Institution | Saitama Medical University |
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Principal Investigator |
Iwasa Kensuke 埼玉医科大学, 医学部, 助手 (00623703)
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| Project Period (FY) |
2018-04-01 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | FFAR4 / ミクログリア / 神経新生 / 神経発達 / 腸脳相関 / 脂質センサー |
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| Outline of Final Research Achievements |
FFAR4 (GPR120) is expressing in the gastrointestinal tract and is a sensor receptor that senses dietary lipids. To reveal the relationship between neuroinflammation and GPR120 signaling, we investigated in GPR120 knockout (KO) mice. In the current study, we discovered notable neuroinflammation (increased PGD2 production and microglial activation) and neurodegeneration (decline in hippocampal volume) in GPR120 KO mice. We also demonstrated that inhibition of PGD2 production attenuated neuroinflammation and neurodegeneration in GPR120 KO hippocampus. These observations reveal the presence of a gut-brain interaction, in that the signaling of dietary lipids are sensed by GPR120, and contributes to hippocampal homeostasis via suppression of neuroinflammation.
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| Academic Significance and Societal Importance of the Research Achievements |
GPR120はDHAやEPAなどのn-3系脂肪酸の受容体である。我々はGPR120機能不全が海馬の神経炎症を引き起こすことを明らかとした。つまり、食事中のn-3系脂肪酸を腸管においてGPR120が感知することが、神経炎症を抑え、脳保護効果を発揮すると考えられる。そして非ステロイド性抗炎症薬（NSAID）によるPGD2産生の阻害が、神経炎症・海馬体積の減少を抑制可能であることも明らかとした。我々の研究結果は、腸管GPR120と神経炎症に関わる新たな腸脳相関の存在を示唆し、またその神経炎症および海馬体積の減少がNSAIDで抑制可能であることを示した。
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