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概日時計複合体は脳脊髄液分泌を操るのか？

生物钟复合体是否控制脑脊液分泌？

基本信息

批准号：
20K16607
负责人：
山口剛史
金额：
$ 2.75万
依托单位：
International University of Health and Welfare
依托单位国家：
日本
项目类别：
Grant-in-Aid for Early-Career Scientists
财政年份：
2020
资助国家：
日本
起止时间：
2020-04-01 至 2024-03-31
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-20K16607/
关键词：
脈絡叢脳脊髄液上皮細胞概日リズム視交叉上核松果体

项目摘要

本研究においては、認知症をきたす原因の一つである突発性正常圧水頭症でみられる脳脊髄液の過剰な貯留が脈絡叢の概日リズムの破綻である可能性を想定して、脈絡叢からの脳脊髄液の産出が概日リズムにより制御されているか、脳内では脈絡叢を含む自律的で異なる周期を発振する組織が互いに作用を及ぼしながら安定した概日リズムを形成しているかについて検討を行った。①脈絡叢の上皮細胞では水チャネルaquaporin1を含む複数の因子の働きにより脳脊髄液が産生されることが報告されている。本研究では、ラット脈絡叢（側脳室、第4脳室）をサンプルに、脈絡叢上皮細胞で発現することが報告されている脳脊髄液産生関連因子のmRNAの発現量において日内変動が見られるかをqRT-PCRにより解析した。その結果、解析した候補因子のうち、グルコーストランスポーター１（Glut1) mRNAの発現に日内変動が認められた。一方、第1候補とした考えていたaquaporin1 mRNAを含むいくつかの因子では日内変動は認められなかったが、おおよそ6時間間隔というウルトラディアンリズムの発現が認められた。②互いに作用を及ぼしながら安定したリズムを形成する脳内の４つの組織として側脳室脈絡叢、第４脳室脈絡叢、視交叉上核、松果体に着目した。組織間の相互作用を検討するため、per2:lucトランスジェニックラットとwildタイプラットから摘出した各組織をそれぞれ組み合わせ共培養下で時計遺伝子per2 mRNAの発現について調査した。しかしながら、どの組み合わせにおいても、異なる周期が概日リズム性の周期に修正されるというような変化は確認できなかった。

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