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

食欲素对反重力肌发育和运动相关功能的调节作用

• 批准号: 16300204
• 负责人: SOYA Hideaki
• 金额: $ 9.22万
• 依托单位: University of Tsukuba
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-16300204/
• 关键词: orexin; hindlimb muscle; alpha-motorneuron; defense Response; emotional stress; ACTH; orexin 1 receptor; orexin 2 receptor; ナルコレプシー; 抗重力筋; ヒラメ筋; プレプロオレキシンノックアウトマウス

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

食欲素(OXs)被认为是下丘脑防御反应中的一种调节因子，即所谓的“打或逃”反应，其特征是伴随着觉醒、下丘脑轴、交感神经系统和α运动神经元(αMN)的激活。这些生理反应是经过精心编排的，参与了体力活动的调节，在“打还是逃”的反应中。我们推测OXs可能同时参与αMN的易化和Hpa轴的激活。为了解决这一问题，我们研究了OX-1R(1型受体)是否在αMN上表达，分别连接到后肢比目鱼肌和指长伸肌。因此，几乎所有到各自肌肉的αMN都有OX-1R。为了确定OXS是否通过OX-1R参与腰椎αMN易化，我们观察了OX-1R拮抗剂预给药后大鼠对水浸泡应激所引起的逃逸游泳反应。…对氧化应激作用的抑制作用αMN上OX-1R的增加降低了逃逸游泳活动。在相同的应激条件下，下丘脑室旁核和下丘脑核内的神经元被激活。预先给予OX-2R拮抗剂可抑制水浸应激所促进的促肾上腺皮质激素释放。在发育过程中，新生儿和婴儿的血浆OX浓度较高，OX-受体在骨骼肌和α-MN上表达。这使我们假设OXS可能通过体液和神经途径来调节骨骼肌的生长和发育。首先，我们检测了前OX基因敲除(KO)小鼠和产仔野生型(Wt)小鼠(10-50周龄)的后肢肌肉重量，发现KO小鼠的足底肌和EDL肌都明显萎缩。此外，我们在体外培养体系中研究了氧合酶对成肌细胞增殖和分化的影响，发现氧合酶可促进成肌细胞的增殖，并通过其特异性受体促进α-MN和HPA轴的双重作用。再次，OXS在体外具有促进成肌细胞增殖的潜在作用。这些结果强调了增食欲素在肌肉发育和运动相关功能中的作用，使我们研究了增食欲素在身体对运动的一些反应和适应中的作用。(349)更少