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ヴァガル感覚神経はベゾルト・ジャリッシュ反射を媒介し,昏睡を引き起こす
Jonathan W Lovelace1,2, Jingrui Ma1,2, Saurabh Yadav1,2
1Department of Neurobiology, University of California, San Diego, CA, USA.
Nature
|November 2, 2023
まとめ
研究者らは,神経ペプチドY受容体Y2 (NPY2R) がベゾルト・ジャリッシュ反射 (BJR) を誘発し,昏睡を引き起こしている静脈神経細胞 (VSN) を特定した. これらのNPY2RVSNを消去すると,BJRが消去され,この神経学的イベントの重要な経路が明らかになりました.
科学分野:
- 神経科学
- 心臓病科
- 生理学
背景:
- 腸内感覚経路は ホメオスタティック・レフレクスのために不可欠であり その機能不全は 神経学的障害と関連しています
- ベゾルト・ジャリッシュ反射 (BJR) は心臓抑制反射であり,ヴァーガル感覚ニューロン (VSN) が関与し,昏睡を引き起こす可能性があると疑われています.
- 心臓のVSNの正確なアイデンティティと機能は,大部分は特徴づけられていない.
研究 の 目的:
- BJRに関与する心臓VSNの分子識別,解剖学的接続,生理学的特徴,および行動的効果を特定する.
- BJRによって引き起こされた 神経回路の解明です
主な方法:
- 単細胞RNAシーケンシングとVSNを特定するためのHYBRiD組織クリアリング
- 特定のVSN群の活性化と抑制のための光遺伝学.
- 高解像度エコーカーディオグラフィー,レーザードップラー流量測定,および生理学的および行動的反応を評価する行動観察.
- 大規模なニューロピクセルによる脳記録と ニューラルネットワーク分析のための機械学習
- NPY2RVSNの特定の消去
主要な成果:
- ニューロペプチドY受容体Y2 (NPY2R) を発現するVSNが特定され,主に心臓の心室壁とポステラ領域を結びました.
- NPY2RVSNの光遺伝的活性化により,BJRトライアード (低血圧,ブラディカルディア,呼吸抑制) とが誘発された.
- 詳細な生理学的および行動的現象は,心臓の出力が低下し,脳の低血流を含む,臨床的シンコープを反映していることが観察されました.
- 神経ネットワークの分析では ニューロンの活動が 広く抑制されていることが分かりました
- 周回関節領域の操作は,昏睡の持続時間と興奮に対するプッシュ・プル効果を示した.
- NPY2RVSNの廃止により,BJRは完全に廃止された.
結論:
- NPY2RVSNは,BJRの原因となる遺伝的に定義された心臓反射経路を形成します.
- この経路は人間のの 重要な生理的,行動的,神経ネットワークの特徴を 正確に再現します
- この発見は,シンコープを理解し,潜在的に治療するための特定の神経基板を提供します.
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