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

食欲素（OXs）被认为是下丘脑防御反应（即“战或逃”反应）中的一种调节因子，其特征是伴随觉醒、hpa -轴、交感神经系统和α -运动神经元（α MN）促进的激活。这些生理反应是精心策划的，参与调节“战斗或逃跑”反应的身体活动。我们假设OXs可能同时参与αMN的促进和hpa轴的激活。为了解决这个问题，我们检测了OX-1R（1型受体）是否分别在连接后肢比目鱼肌和指长伸肌（EDL）的αMN上表达。因此，几乎所有的αMN到各自的肌肉都有OX-1R。为了确定OXs是否通过OX-1R参与了腰椎α mn的促进作用，我们检测了OX-1R拮抗剂预处理后大鼠浸泡在水中对应激的逃逸游泳反应。过量的OX-1R对αMN的抑制作用降低了OXs的逃逸游泳活性。在相同的应激条件下，PVN和LHA神经元均被激活。经预处理的OX-2R（2型受体）拮抗剂可抑制浸水应激促进的ACTH释放。新生儿和婴儿在发育过程中血氧饱和度较高，骨骼肌和αMNs中有氧受体表达。这导致我们假设OXs通过体液和神经元途径介导骨骼肌的生长和发育。首先，我们检测了pre - pro- ox敲除（KO）小鼠和同窝野生型（Wt）小鼠（10-50周龄）的后肢肌肉重量，发现KO小鼠的跖肌和EDL肌肉都明显萎缩。此外，我们在体外培养系统中考察了OXs对成肌细胞增殖和分化的影响，发现OXs加速了成肌细胞的增殖。我们发现OXs通过其特异性受体发挥促进αMN和hpa -轴的双重作用。再次，OXs在体外促进成肌细胞增殖中发挥潜在作用。这些结果强调了食欲素在肌肉发育和运动相关功能中的作用，引导我们研究食欲素在身体对运动的某些反应和适应中的作用。少(349)

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