Impact of histaminergic H3 receptor antagonist on hypoglossal nucleus in chronic intermittent hypoxia conditions.

RATIONALE: 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.

OBJECTIVES: The aim of the study was to investigate the role histaminergic neurons play in the regulation of the genioglossus.

METHODS: 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.

RESULTS: 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.

CONCLUSIONS: 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.