Influence of hypercapnia on the synthesis of neuropeptides and their receptors in murine brain

Background and objective: Sleep disorders are a complicated and major public health concern affecting millions of individuals. Obstructive sleep apnoea (OSA) is a common but still under‐recognized disease which can cause intermittent nocturnal hypercapnia. Neuropeptides play critical roles in neurotransmission, acting as transmitters or modulators. Results from recent studies have implicated several neuropeptides in sleep and breathing regulation, including orexin, neuropeptides Y and galanin. Therefore, the present study aimed to evaluate the influence of hypercapnia on these neuropeptides and their receptors in order to assess their potential role in the pathogenesis of OSA. Methods: Fifteen C57BL/6J mice were randomly divided into three groups and exposed to moderate hypercapnia (5% CO₂ with balanced room air), or severe hypercapnia (10% CO₂ with balanced room air) or room air for 3 h (9:00–12:00 h), respectively. Immediately following exposure the brainstem and hypothalamus were excised for real‐time reverse transcription polymerase chain reaction and western blot analyses. Results: In the hypothalamus gene expression including galanin, orexin and neuropeptide Y receptor 1 (NPYR1) was downregulated by hypercapnia. However, protein and mRNA levels of orexin‐A receptor were upregulated by severe hypercapnia. In the brainstem only NPYR1 mRNA expression was decreased in moderate hypercapnia compared with that in severe hypercapnia. Conclusions: These findings suggest that hypercapnia can affect these neuropeptides and their receptors, especially the orexin and orexin‐A receptor. The potential relationships between these peptides and OSA are worthy of further investigation.