下垂体-下垂体-副腎軸の断食時の活性化のための神経基礎
Amelia M Douglass1, Jon M Resch1,2, Joseph C Madara1
1Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Nature
|July 26, 2023
まとめ
断食は下垂体にある AgRPニューロンを活性化させ ストレス反応に不可欠です これらのニューロンはHPA軸を抑制し GABAergic信号を抑制し,飢餓とは関係ありません.
科学分野:
- 神経科学
- 内分泌学
- メタボリズム
背景:
- 断食は生存のための適応を誘発し,下垂体-腎上腺 (HPA) 軸の活性化を含みます.
- 断食中のHPA軸の活性化を誘発する神経メカニズムは,ほとんど不明である.
- Agouti関連ペプチド (AgRP) を発現するニューロンは,飢餓の調節因子として知られていますが,ストレス反応におけるその役割は不明です.
研究 の 目的:
- 断食によるHPA軸の活性化に伴う神経メカニズムを解明する.
- 断食に対するHPA軸の反応におけるAgRPニューロンの役割を決定する.
- AgRPニューロンがニューロン活動を調節する新しい経路を特定する.
主な方法:
- AgRPニューロンの遺伝子操作を 断食モデルで利用した
- AgRPニューロンからパラベントリカル下垂体 (PVH) へのニューロンの投影を調査した.
- AgRPニューロン媒介のHPA軸活性化におけるGABAergicシグナル伝達とGABA- B受容体の役割を調べました.
主要な成果:
- 断食で活性化されたAgRPニューロンは,HPA軸の活性化に不可欠です.
- AgRPニューロンはPVHに投射され,ストリア・ターミナリス (BNST) の床核からのGABAergicアフェレンツをプレシナプス的に阻害する.
- PVH内のコルチコトロフィン放出ホルモン (CRH) を発現するニューロンのこの無抑制は,飢餓誘導とは独立してHPA軸を活性化します.
結論:
- AgRPニューロンは,断食によるHPA軸の活性化の主な原動力として特定されました.
- 阻害性アファレントのプレシナプス阻害によるニューロン活性化の新しいメカニズムを発見した.
- BNST阻害トーン低下が,空腹とストレスによるHPA軸の活性化の一般的な経路である可能性を示唆しています.
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