リズム的なシリアの変化は,生体時計におけるSCNニューロン連動性をサポートする

Hai-Qing Tu¹, Sen Li¹, Yu-Ling Xu¹

¹Nanhu Laboratory, National Center of Biomedical Analysis, Beijing, China.

Science (New York, N.Y.)

|June 1, 2023

まとめ

上核 (SCN) にある主要な毛皮は,内臓時計の維持に欠かせないものです

科学分野:

神経科学
クロノバイオロジー
細胞生物学

背景:

上神経核 (SCN) は哺乳類の生理リズムを調整する主日時計である.
SCNニューロンの間の細胞間結合は,日中時計の一貫性と強さを維持するために不可欠です.
周囲の環境の乱れによって日常リズムが乱れることもあり時計の安定性を確保するメカニズムが必要であることを強調しています

研究の目的:

SCN内の細胞間結合におけるプライマリシリアの役割を調査する.
特定のSCNニューロンのプライマリシリアが,内部の生理時計の強さに寄与するかどうかを判断する.
シリアがSCN機能に影響を与えるSonic Hedgehog (Shh) 信号を含む分子メカニズムを解明する.

主な方法:

ネズミのニューロメディンS産生 (NMS) ニューロンにおけるシリオゲネシスの遺伝的消去を活用した.
シリアの欠乏がシミュレートされたジェットラグ条件下での昼間時計の相変化に与える影響を評価した.
シリア欠乏性のスライスにおける個々のSCNニューロンの昼夜リズムを分析し,ソニック・ヘッジホッグ (Shh) 信号伝達経路を調査した.

主要な成果:

NMSニューロンのプライマリーシリアは,数量と長さのサーカディアンリズムを示します.
NMSニューロンのシリアの遺伝的消去は,ジェットラグ条件下で急速な内部クロック・フェーズシフトをもたらした.
シリアが欠けていたSCNニューロンは,外部の干渉の後に非同期的なリズムを示し,Shh信号の不活性化はシリアの消去効果を模倣した.

結論:

主要なシリアはSCNニューロン間の細胞間結合に不可欠であり,堅固な昼夜時計機能を保証する.
シリアのリズムの変化は,SHH信号とクロック遺伝子発現を調節し,昼夜一貫性に寄与する.
SCNにおけるシリア媒介のShhシグナリングは,環境障害に対する内部クロックの安定性を維持するための重要なメカニズムである.

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