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麻醉小鼠的 Kölliker-Fuse 核中食欲素-2 受体的激活会导致呼吸频率短暂减慢。

Activation of orexin-2 receptors in the Kӧlliker-Fuse nucleus of anesthetized mice leads to transient slowing of respiratory rate.

作者信息

Varga Adrienn G, Whitaker-Fornek Jessica R, Maletz Sebastian N, Levitt Erica S

机构信息

Department of Pharmacology and Therapeutics, University of Florida, Gainesville, FL, United States.

Breathing Research and Therapeutics Center, University of Florida, Gainesville, FL, United States.

出版信息

Front Physiol. 2022 Nov 2;13:977569. doi: 10.3389/fphys.2022.977569. eCollection 2022.

Abstract

Orexins are neuropeptides originating from the hypothalamus that serve broad physiological roles, including the regulation of autonomic function, sleep-wake states, arousal and breathing. Lack of orexins may lead to narcolepsy and sleep disordered breathing. Orexinergic hypothalamic neurons send fibers to Kӧlliker-Fuse (KF) neurons that directly project to the rostroventral respiratory group, and phrenic and hypoglossal motor neurons. These connections indicate a potential role of orexin-modulated KF neurons in functionally linking the control of wakefulness/arousal and respiration. In a reduced preparation of juvenile rats Orexin B microinjected into the KF led to a transient increase in respiratory rate and hypoglossal output, however Orexin B modulation of the KF in intact preparations has not been explored. Here, we performed microinjections of the Orexin B mouse peptide and the synthetic Orexin 2 receptor agonist, MDK 5220, in the KF of spontaneously breathing, isoflurane anesthetized wild type mice. Microinjection of Orexin-2 receptor agonists into the KF led to transient slowing of respiratory rate, which was more exaggerated in response to Orexin-B than MDK 5220 injections. Our data suggest that Orexin B signaling in the KF may contribute to arousal-mediated respiratory responses.

摘要

食欲素是源自下丘脑的神经肽,具有广泛的生理作用,包括调节自主功能、睡眠-觉醒状态、唤醒和呼吸。缺乏食欲素可能导致发作性睡病和睡眠呼吸障碍。产生食欲素的下丘脑神经元向直接投射到吻侧腹侧呼吸组以及膈神经和舌下运动神经元的 Kölliker-Fuse(KF)神经元发送纤维。这些连接表明食欲素调节的 KF 神经元在功能上连接觉醒/唤醒控制和呼吸方面可能发挥作用。在幼年大鼠的简化制备中,向 KF 微量注射食欲素 B 会导致呼吸频率和舌下输出短暂增加,然而完整制备中食欲素 B 对 KF 的调节尚未得到探索。在此,我们在自发呼吸、异氟烷麻醉的野生型小鼠的 KF 中微量注射了食欲素 B 小鼠肽和合成的食欲素 2 受体激动剂 MDK 5220。向 KF 微量注射食欲素 2 受体激动剂会导致呼吸频率短暂减慢,与注射 MDK 5220 相比,对食欲素 B 的反应更为明显。我们的数据表明,KF 中的食欲素 B 信号可能有助于唤醒介导的呼吸反应。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/72a3/9667107/398de616460b/fphys-13-977569-g001.jpg

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