Physiology relevance of cerebral lymphatic flow and the mechanism of higher brain dysfunction due to its breakdown

2020 Fiscal Year Final Research Report

• Project/Area Number: 18H02606
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 48030:Pharmacology-related
• Research Institution: Keio University
• Principal Investigator: Masato Yasui 慶應義塾大学, 医学部(信濃町), 教授 (90246637)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: アクアポリン / 脳リンパ排泄 / 非線形光学 / アルツハイマー病

Outline of Final Research Achievements

Lymphatic flow was thought to be absent in the brain, but it has recently been shown that glial cells, especially aquaporin 4 (AQP4), may play a role. Here we succeeded in visualizing the water dynamics of brain tissue by observing the water molecules themselves using a nonlinear optical microscope that we originally developed.
Abnormal lymphatic excretion in the brain leads to abnormal accumulation of amyloid β (Aβ), and its involvement with Alzheimer's disease is suspected. By crossing an Alzheimer's disease mouse model with an AQP4-deficient mouse, we found that the mice showed marked abnormal behavior at an early stage. These results are expected to lead to the development of new early diagnosis and treatment methods for Alzheimer's disease.

Free Research Field

神経科学

Academic Significance and Societal Importance of the Research Achievements

本研究成果は、AQP4の発現や機能を維持することで、アルツハイマー病の進行を遅らせ、更には改善を図るというこれまでとは全く異なる治療戦略の創出を促す可能性がある。また、脳のリンパ排泄機構を直接可視化する技術の向上をもたらすと考えられ、将来的な特異的な造影技術の開発と相まって、様々な脳疾患の診断法の発展、中枢神経に作用する薬物の動態の可視化及び制御に関する革新的な技術開発につながると期待される。脳のリンパ排泄機構の理解は脳アミロイド血管症やその他の神経変性疾患の理解にもつながり、認知症にとどまらず今後益々高齢化が進む我が国の社会的負担を大幅に軽減するとともに国民の福祉の向上にも大きく寄与する。