Cardiorespiratory control during sleep in orexin deficient mice

Aim of this thesis was to study specific aspects of cardiorespiratory control during sleep in orexin- deficient (ORX-KO) mice. In particular, we explored the autonomic mechanisms of cardiovascular control during sleep in ORX-KO mice, and we investigated the role of orexins (ORXs) in breathing regulation and disturbances during sleep, as a function of Ta (ambient temperature). To unravel the mechanisms of ORX-dependent cardiovascular changes during sleep, we recorded electroencephalogram, electromyogram and arterial pressure (AP) in 13 male ORX-KO mice and 12 wild-type (WT) mice during intraperitoneal infusions of selective autonomic blockers. To investigate the role of ORXs in breathing as function of sleep states and Ta, we studied 9 male ORX-KO and 8 WT mice at two different Ta (30°C, 20°C) in a whole-body plethysmography chamber. ORX-KO mice had higher AP values during rapid-eye-movement sleep (REMS), smaller decreases in AP from wakefulness (W) to both non-rapid-eye-movement sleep (NREMS) or REMS, and greater increases in AP from NREMS to REMS, compared to WT. These differences were abolished by prazosin and, also by atenolol, except for the transition from W to REMS, in ORX-KO mice. No significant differences were found in respiratory regulation during sleep between WT and ORX-KO mice, except for sigh occurrence rate, which was increased at Ta=20°C, compared with Ta=30°C, only in WT mice. In both groups, the occurrence rate of sleep apneas in NREMS was significantly reduced at Ta=20°C. We demonstrated that changes in cardiovascular sympathetic control mediate sleep-related alterations of AP showed by ORX-KO mice, compared to WT mice. Moreover, we demonstrated that the sleep apnea occurrence rate critically depends on Ta, and that ORXs have not a main role in sleep-breathing regulation as a function of Ta.