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2023 Fiscal Year Final Research Report

The Role of Brain Bile Acids in Neurological Diseases

Research Project

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Project/Area Number 20K16497
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 51030:Pathophysiologic neuroscience-related
Research InstitutionOsaka University

Principal Investigator

Sugiyama Shintaro  大阪大学, 大学院医学系研究科, 招へい教員 (50839636)

Project Period (FY) 2020-04-01 – 2024-03-31
Keywords肝-脳連関機構 / 脳梗塞 / Tight junction / Claudin3 / 胆汁酸 / Claudin5 / occludin / Tricellulin
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.

Free Research Field

脳梗塞

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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Published: 2025-01-30  

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