Orexins: Relation Between Sleeping, Eating, and Breathing

Prabha      Kc; Musa   A.   Haxhiu; Kannan   V.   Balan

Abstract

Orexins (orexin-A and orexin-B) are produced in the lateral hypothalamic area, also known as the feeding center, have been implicated to play a critical role in central regulation and maintenance of sleep and wakefulness state, feeding and energy homeostasis by acing upon its receptors (orexin receptor 1 and orexin receptor 2) respectively. Orexin neurons are active during wakefulness period and exert an excitatory influence on monoaminergic-containing neurons, which are known to play an important role during arousal. Deficiency of orexin causes narcolepsy and fragmentation in sleep pattern. Orexinergic neurons senses bodys external as well as internal environments and are also sensitive to metabolic cues indicating that theses neurons are involved in coordinating the feeding behavior and behavioral vigilance states for its survival. Orexin stimulates both feeding and metabolic rate and its deficiency leads to altered energy homeostasis, including decreased caloric intake with an increased body mass index as seen in narcoleptic patients. Experimental studies have shown that orexins have a role in regulating autonomic function; increase in blood pressure and heart rate following orexin administration suggests that orexins stimulates sympathetic outflow. It has also been shown that orexin decreases upper airway resistance during inspiration and maintains CO2 sensitivity during wake period suggesting its importance in state dependent control of the airways. Therefore, these findings suggest that orexinergic neurons provide a crucial link between arousal and energy balance, and modulate breathing in physiological state dependent manner.

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