Department of Pharmacology and Physiology, George Washington University, Washington, DC 20037, USA.
Division of Pulmonary and Critical Care Medicine, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Sleep. 2023 Apr 12;46(4). doi: 10.1093/sleep/zsad009.
Clinical studies have shown that oxytocin administered intranasally (IN) decreased the incidence and duration of obstructive events in patients with obstructive sleep apnea (OSA). Although the mechanisms by which oxytocin promotes these beneficial effects are unknown, one possible target of oxytocin could be the excitation of tongue-projecting hypoglossal motoneurons in the medulla, that exert central control of upper airway patency. This study tested the hypothesis that IN oxytocin enhances tongue muscle activity via the excitation of hypoglossal motoneurons projecting to tongue protrudor muscles (PMNs). To test this hypothesis we performed in vivo and in vitro electrophysiological studies in C57BL6/J mice as well as fluorescent imaging studies in transgenic mice in which neurons that express oxytocin receptors co-express fluorescent protein. IN oxytocin significantly increased the amplitude of inspiratory-related tongue muscle activity. This effect was abolished by severing the medial branch of hypoglossal nerve that innervates PMNs of the tongue. Oxytocin receptor-positive neurons were more prevalent in the population of PMNs than in retractor-projecting hypoglossal motoneurons (RMNs). Oxytocin administration increased action potential firing in PMNs, but had no significant effect on firing activity in RMNs. In conclusion, IN oxytocin stimulates respiratory-relating tongue muscle activity likely acting on central hypoglossal motoneurons that provide tongue protrusion and upper airway opening. This mechanism may play a role in oxytocin-induced reductions in upper airway obstructions in patients with OSA.
临床研究表明，经鼻给予催产素（IN）可降低阻塞性睡眠呼吸暂停（OSA）患者阻塞性事件的发生率和持续时间。虽然催产素促进这些有益效果的机制尚不清楚，但催产素的一个可能靶点可能是刺激延髓中投射到舌的舌下运动神经元，从而对上呼吸道通畅发挥中枢控制作用。本研究通过在 C57BL6/J 小鼠中进行体内和体外电生理研究以及在表达催产素受体的神经元共表达荧光蛋白的转基因小鼠中进行荧光成像研究，检验了 IN 催产素通过兴奋投射到舌突出肌（PMN）的舌下运动神经元来增强舌肌活动的假设。为了验证这一假设，我们在 C57BL6/J 小鼠中进行了体内和体外电生理研究，并在表达催产素受体的神经元共表达荧光蛋白的转基因小鼠中进行了荧光成像研究。IN 催产素显著增加了吸气相关舌肌活动的幅度。这一效应被切断支配舌 PMN 的舌下神经内侧支所消除。在 PMN 中，催产素受体阳性神经元比投射到舌回缩肌的舌下运动神经元（RMN）更为常见。催产素给药增加了 PMN 的动作电位放电，但对 RMN 的放电活动没有显著影响。总之，IN 催产素刺激呼吸相关的舌肌活动，可能作用于提供舌突出和上呼吸道开放的中枢性舌下运动神经元。这种机制可能在催产素诱导的 OSA 患者上呼吸道阻塞减少中发挥作用。
