中枢性睡眠呼吸暂停或低通气主要是由于中枢性呼吸驱动力减弱所致，而中枢呼吸化学感受器功能异常是呼吸驱动减弱的重要因素。近年研究发现，瘦素信号系统具有易化呼吸化学感受器反射，改善睡眠相关性低通气的作用，但此作用的中枢靶点和相关的分子神经机制尚待明确，尤其是作为中枢呼吸化学感受器的孤束核，其瘦素系统对呼吸的调控作用亟待深入研究。因此，我们提出如下假说：激活孤束核瘦素信号通路可增强中枢性呼吸驱动，易化中枢呼吸化学感受器反射，此作用主要是通过JAK2/STAT3途径实现的。本课题将观察：选择性刺激孤束核表达瘦素受体的神经元亚群是否增强肺通气或膈神经活动；敲除孤束核瘦素受体是否减弱中枢呼吸化学感受器反射；JAK2/STAT3信号途径是否参与了瘦素易化呼吸的效应。研究结果将揭示孤束核瘦素信号参与呼吸调控的分子神经机制，为精准干预中枢性睡眠呼吸暂停或低通气提供分子水平的靶点。

Central sleep apnea or hypoventilation is ascribed mainly to impairment of respiratory drives and dysfunctions of central respiratory chemoreceptors contribute to reduced respiratory drives. Recent studies demonstrate that leptin signaling facilitates respiratory chemoreceptor reflexes and improves sleep-related hypoventilation, whereas the central targets and molecular mechanisms involved remain to be unveiled. In particular, attempt should be made to investigate effect of leptin on breathing in the nucleus tractus solitarii (NTS) as an important chemoreceptor. We therefore hypothesize that the activation of leptin signaling in the NTS contributes to potentiation of central respiratory drives and facilitation of central respiratory chemoreceptors. Toward this end, we seek to examine whether optogenetic or chemogenetic stimulation of leptin receptor-containing NTS neurons potentiates ventilation or phrenic nerve activity, to test whether leptin receptor deletion in NTS neurons impairs central respiratory chemoreflex, to test if the JAK2/STAT3 signaling molecules are recruited for leptin’s role. The outcomes would be expected to reveal molecular mechanism underlying leptin’s action on breathing and meanwhile, to identify molecular targets for precise treatment of central sleep apnea or hypoventilation.