エンジオテンシン変換酵素ゲート脳回路特異的な可塑性

Brian H Trieu^1,2, Bailey C Remmers³, Carlee Toddes¹

¹Graduate Program in Neuroscience, University of Minnesota Medical School, Minneapolis, MN, USA.

Science (New York, N.Y.)

|February 24, 2022

まとめ

脳内のアニオテンシン変換酵素 (ACE) 阻害は,自然な疼痛緩和経路を強化します. このアプローチは,報酬や依存症を引き起こすことなく,痛みや依存症の臨床的利点を提供することができます.

科学分野:

神経科学
薬理学について
生物化学

背景:

アンジオテンシン変換酵素 (ACE) は,血圧の調節に不可欠です.
ACEは脳の状組織に豊富に存在するが,その特定の機能は不明である.
神経学的な研究において,線状回路におけるACEの役割を理解することは不可欠です.

研究の目的:

マウスのアキュンベンス核におけるACEの機能を調査する.
オピオイドシグナル伝達とニューロンの活動に対するACE阻害の影響を決定する.
薬物中毒と社会的行動における ACE阻害の治療の可能性を探るため

主な方法:

マウス核アクンベンスのACEによるMet-enkephalin-Arg-Pheの分解を調査した.
μ- オピオイド受容体の活性化に対するACE阻害の影響を調査した.
ドーパミン受容体発現ニューロンへのグルタミン酸の放出の変化を評価した.
条件づけられた場所の好みと社会的相互作用のテストを用いてACE抑制の行動効果を評価した.

主要な成果:

ACEは,エンケファリンヘプタペプチドであるMet-enkephalin-Arg-Pheを分解することが判明しました.
このペプチドによるACE抑制はμ- オピオイド受容体の活性化を高めました.
これは特定の中等脊髄神経にグルタミン酸の放出を減少させた.
システミックACE阻害はフェンタニル誘発の報酬を低下させ,社会的相互作用を改善した.

結論:

中央ACE阻害はペプチドの分解を防ぐことによって内在的なオピオイドシグナル伝達を調節する.
脳内のACEをターゲットにすることで痛みの管理と依存症の治療に新しい戦略が提供されるかもしれません
このアプローチは,中毒のリスクを軽減しながら,臨床的な利点の可能性を示しています.

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