Regulatory role by orexin on the development of anti-gravity muscle and exercise-related functions

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Orexins (OXs) have been known as a hypothalamic regulating factors in the defense response, so called "fight or flight" response, which is characterized by a concomitant activation in arousal, HPA-axis, sympathetic nerve system and alpha-motoneurons (α MN) facilitation. These physiological reactions are orchestrated to involved in the regulation of physical activity in "fight or flight" response. We hypothesized that OXs would simultaneously be involved in the αMN facilitation and HPA-axis activation. To address this, we examined whether OX-1R (type-1-receptor) expresses on αMN, connecting to hindlimb soleus and extensor digitorum longus (EDL) muscle, respectively. As a result, almost all αMN to their respective muscles had OX-1R. To identify whether OXs were involved in the αMN-facilitation via OX-1R in lumbar, we examined the escape swimming response to stress provoked by immersing rats into water after pretreatment of OX-1R antagonist administration. The inhibition of OXs action via … More OX-1R on αMN decreased the escape swimming activity. Under the same stress, neurons in PVN and LHA were activated. ACTH release which promoted by water immersion stress was suppressed by pretreatment of OX-2R (type-2-receptor) antagonist administration.Plasma concentrations of OXs were higher in neonates and infant during decelopment, and OX-receptors express on skeletal muscles and αMNs. It leads us hypothesized that OXs would mediate growth and development of skeletal muscle through both humoral and neuronal pathways. First, we examined hind limb muscular weight between prepro-OX knock-out (KO) mice and littermate wild-type (Wt) mice (10-50 weeks-old), and found that both plantaris and EDL muscles in KO mice atrophied significantly. In addition, we investigated the effects of OXs on the proliferation and defferentation of myoblasts in vitro culture system, and found that OXs accelerated the proliferation of myoblasts.We found that OXs plays dual roles for facilitating αMN and the HPA-axis through their specific receptors. Again, OXs play a potential role to promote myoblasts' proliferation in vitro. These results underscore orexin's role in muscular development and exercise-related functions, leading us to examine the role of orexin on some response and adaptation of body to exercise. (349) Less