Effect of ambient temperature on sleep breathing phenotype in mice: the role of orexins

The loss of orexinergic neurons, which release orexins, results in narcolepsy. Orexins participate in the regulation of many physiological functions, and their role as wake-promoting molecules has been widely described. Less is known about the involvement of orexins in body temperature and respiratory regulation. The aim of this study was to investigate if orexin peptides modulate respiratory regulation as a function of ambient temperature (Ta) during different sleep stages. Respiratory phenotype of male orexin knockout (KO-ORX, N=9) and wild-type (WT, N=8) mice was studied at thermoneutrality (Ta=30°C) or during mild cold exposure (Ta=20°C) inside a whole-body plethysmography chamber. The states of wakefulness (W), non-rapid eye movement sleep (NREMS) and rapid eye movement sleep (REMS) were scored non-invasively, using a previously validated technique. In both WT and KO-ORX mice, Ta strongly and significantly affected ventilatory period and minute ventilation values during NREMS and REMS; moreover, the occurrence rate of sleep apneas in NREMS was significantly reduced at Ta=20°C compared with Ta=30°C. Overall, there were no differences in respiratory regulation during sleep between WT and KO-ORX mice, except for sigh occurrence rate, which was significantly increased at Ta=20°C compared with Ta=30°C in WT mice, but not in KO-ORX mice. These results do not support a main role for orexin peptides in the temperature-dependent modulation of respiratory regulation during sleep. However, we showed that the occurrence rate of sleep apneas critically depends on Ta, without any significant effect of orexin peptides.