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中枢神経系の小動脈の洞穴は神経血管結合を媒介する
Brian W Chow1, Vicente Nuñez1, Luke Kaplan1
1Department of Neurobiology, Harvard Medical School, Boston, MA, USA.
Nature
|February 21, 2020
まとめ
動脈内皮細胞は,ENOS-NOシグナル伝達から独立した経路である豊富な洞窟を通して神経血管結合を積極的に媒介する. この発見は 脳の血流を制御する 新しいメカニズムを明らかにしています
科学分野:
- 神経科学
- 血管生物学
- 細胞メカニズム
背景:
- 神経血管結合は 脳のエネルギー需要と 血流を合わせます これは脳の機能と 機能的イメージングに不可欠です
- 神経血管結合の障害は 神経退行性疾患と関連していますが そのメカニズムは十分に理解されていません
- 従来のモデルは,神経細胞またはアストロサイト由来因子が,滑らかな筋肉細胞を通して動脈を直接拡張すると仮定しています.
研究 の 目的:
- 神経血管結合の細胞と分子メカニズムを調査する
- 神経血管結合を媒介する動脈内皮細胞 (aECs) の役割を決定する.
- 特定の経路,特に洞窟とENOS-NO経路の貢献を明らかにする.
主な方法:
- 覚醒したマウスの脳皮質における 神経活動と血管動力の2フォトン顕微鏡検査
- aECsの洞窟を排除し,または内皮 NO合成酵素 (eNOS) を消去するための急性遺伝的干渉.
- 遺伝子操作後の神経血管結合機能の評価
主要な成果:
- 動脈内皮細胞 (aECs) は,他の中枢神経内皮細胞とは異なり,豊富な洞窟を持っています.
- 特にaECsのカヴェーラを除去すると,神経血管結合が損なわれ,隣接する滑らかな筋肉細胞は保存されます.
- aECの洞穴介質経路は,ENOS-NO経路から大きく独立しています.
- カヴェーラとeNOSを併用すると,神経血管結合が完全に廃止され,カヴェーラ経路の主要な役割が示されました.
結論:
- 動脈内皮細胞 (aECs) は神経血管結合を媒介する重要な役割を果たします.
- aECにおける新しい洞窟依存経路は,脳血流の調節に大きく貢献する.
- この経路は中央神経系からの信号を活性化して 血管拡張のための滑らかな筋肉細胞に伝達します
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