Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, 180 Fenglin Rd., Shanghai, 200032, China.
Clinical Centre for Sleep Breathing Disorders and Snoring, Zhongshan Hospital, Fudan University, Shanghai, China.
Psychopharmacology (Berl). 2021 Jan;238(1):121-131. doi: 10.1007/s00213-020-05663-0. Epub 2020 Sep 22.
The hypoglossal nucleus (HN) controls the movement of the genioglossus (GG) muscle whose dysfunction leads to airway occlusion and occurrence of obstructive sleep apnea (OSA). Histamine produced by the tuberomammillary nucleus (TMN) has a potent excitatory action on GG muscle activity.
The aim of the study was to investigate the role histaminergic neurons play in the regulation of the genioglossus.
C57BL/6 mice were exposed to chronic intermittent hypoxia (CIH) for 3 weeks to resemble OSA. The histamine H3 receptor (H3R) antagonist ciproxifan was applied to increase histamine in the brain. Histamine levels and GG activity were measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and electromyogram (EMG) separately. Neuronal activity and repair ability of the HN and TMN and key proteins of histamine were analyzed by immunohistochemistry and western blots.
Significant decline of histamine level and GG activity of the HN and TMN induced by CIH exposure could be ameliorated by ciproxifan. Application of ciproxifan could also partly reverse the decline of the histidine decarboxylase (HDC) by CIH.
This investigation studied the impacts of ciproxifan on the HN and TMN in CIH conditions and revealed that the negative effects on the HN and TMN caused by CIH could be partly ameliorated by ciproxifan, which might open new perspectives for the development of pharmacological treatment for OSA.
舌下神经核（HN）控制颏舌肌（GG）的运动，其功能障碍可导致气道阻塞和阻塞性睡眠呼吸暂停（OSA）的发生。结节乳头核（TMN）产生的组胺对 GG 肌肉活动具有很强的兴奋作用。
本研究旨在探讨组胺能神经元在调节颏舌肌中的作用。
将 C57BL/6 小鼠暴露于慢性间歇性低氧（CIH）3 周，以模拟 OSA。应用组胺 H3 受体（H3R）拮抗剂西普昔芬增加脑中组胺。通过液相色谱-串联质谱（LC-MS/MS）和肌电图（EMG）分别测量组胺水平和 GG 活性。通过免疫组织化学和 Western blot 分析 HN 和 TMN 的神经元活性和修复能力以及组胺的关键蛋白。
CIH 暴露引起的 HN 和 TMN 中组胺水平和 GG 活性的显著下降可被西普昔芬改善。西普昔芬的应用也可部分逆转 CIH 引起的组氨酸脱羧酶（HDC）下降。
本研究研究了西普昔芬对 CIH 条件下 HN 和 TMN 的影响，揭示了 CIH 对 HN 和 TMN 的负面影响可部分被西普昔芬改善，这可能为 OSA 的药物治疗开辟新的前景。
