2023 Fiscal Year Final Research Report
The Role of Brain Bile Acids in Neurological Diseases
| Project/Area Number |
20K16497
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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 51030:Pathophysiologic neuroscience-related
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| Research Institution | Osaka University |
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Principal Investigator |
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| Project Period (FY) |
2020-04-01 – 2024-03-31
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| Keywords | 肝-脳連関機構 / 脳梗塞 / Tight junction / Claudin3 / 胆汁酸 / Claudin5 / occludin / Tricellulin |
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| Outline of Final Research Achievements |
The purpose of this study was to identify novel transmitters of the liver-brain interface from the viewpoint of the epithelial cell barrier, and to elucidate the regulatory mechanism, physiological significance, and pathophysiological relationship of the liver-brain interface. Cldn3KO mice showed no increase in cerebral infarct volume. Cldn3, Cldn5 and occludin cooperated to regulate BBB in cerebral infarction. occludin KO mice showed decreased expression of Cldn5 and ZO-1, increased infarct volume and extravascular leakage after cerebral infarction, and induced BBB dysfunction from acute to chronic phase, angiogenesis was also suppressed, leading to neurological deterioration.
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| Free Research Field |
脳梗塞
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| Academic Significance and Societal Importance of the Research Achievements |
occludinは生体内で虚血性脳卒中後の急性期から慢性期にかけて重要な役割を果たすことが明らかになった。また、Cldn3KOマウス、Cldn2/3dKOマウス、occludin KOマウスを解析していく中で、Cldn3/2/5とMARVEL family のoccludin、Tricellulin及び裏打ち蛋白であるZO-1が、想定以上に、相互に強く連携しながらタイトジャンクションを形成していることが分かった。
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