Does the circadian clock complex control cerebrospinal fluid secretion?

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K16607
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 52020:Neurology-related
• Research Institution: International University of Health and Welfare
• Principal Investigator: Yamaguchi Takeshi 国際医療福祉大学, 保健医療学部, 助教 (50726510)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: 脈絡叢 / 脳脊髄液 / 概日時計

Outline of Final Research Achievements

Excessive accumulation of cerebrospinal fluid is seen in the patients with sudden normal pressure hydrocephalus, which is one of the causes of dementia. This excessive accumulation is most likely attributed to a disruption of circadian rhythms in the choroid plexus. Thus, we investigated diurnal variation of expression of genes which are responsible for the production of cerebrospinal fluid.
As a result, among the candidate genes that hypothetically control circadian rhythm in the cerebrospinal fluid production, only Glut1 mRNA expressed in a diurnal variation pattern. No significant diurnal variation was observed for other candidate genes, but some genes (AQP1, NKCC1, and Claudin2) expressed in a fluctuating manner with a cycle of about 6 hours. On the other hand, significant diurnal variation was shown in the expression of AQP1 and Claudin2 proteins in the fourth ventricular choroid plexus.

Free Research Field

神経科学

Academic Significance and Societal Importance of the Research Achievements

睡眠障害の患者が認知症の最も多い原因疾患であるアルツハイマー病（AD）を発症しやすい点から、概日リズムの乱れがADと関連していると考えられる。近年、AD予防のメカニズムとして脳脊髄液の環流によるアミロイドβの洗い流しが注目を集めている。休眠期に拡張される間質腔に脳脊髄液を押し流す力の変動が概日時計によって制御され、脳内でのアミロイドβの排除が促進されると考えている。脳脊髄液環流に対する概日時計の制御機構の詳細を解明することは、脳内からの老廃物除去の障害がもたらす様々な疾患への予防に対する時間医学への応用に繋がることを期待している。