NEURAL-THYROID INTERACTION ON ISOMYOSIN EXPRESSION

描述：（申请人摘要）本项目的目标是 研究重力、神经支配和甲状腺的相互作用 激素（T3）在肌球蛋白重链发育程序中的作用 (MHC)新生啮齿动物抗重力和运动能力中同种型表达 骨骼肌。有待检验的中心假设是， 对发展和维持缓慢的 (type I）抗重力和运动肌中的MHC表达，使得 在缺乏它的情况下，大量的肌肉细胞上调了 由于对甲状腺的反应性增加， 激素.相反，快速IIx和IIb的正常表达 MHC的发育调节与重力无关，但需要 完整的神经和T3的存在，以使这些亚型 通过替换新生儿MHC达到表达的完全成熟 同种型。另一个目的是确定肌肉是否 在没有重力的情况下，发展会产生有害的反应， 从而在新生儿状态下从暴露于微重力中恢复， 导致对肌肉质量和成人模式的不可逆影响， 肌球蛋白亚型表达。为了验证这些假设，双方都 对照和微重力暴露的新生大鼠（从2-3天开始 年龄）将被分配到以下亚组：正常对照组; 失神经支配（DEN）;甲状腺缺陷（TD）; DEN + TD。的 微重力暴露的新生动物（沿着哺乳母鼠）将 在航天飞机上进行航天飞行（神经实验室使命）， 18-21天。恢复期（以及恢复后3-4周），飞行 动物和地面控制将被处理，以便关键肌肉将 研究MHC亚型在mRNA和蛋白质水平的表达 使用电泳、免疫组织化学和免疫组织化学的分析水平 原位杂交技术总的来说，这些实验将 明确界定这些关键因素各自的相互作用 对肌肉发育有很强的影响 和收缩蛋白表达。

DESCRIPTION: (Applicant's abstract) The goal of this project is to examine the interactive role of gravity, innervation, and thyroid hormone (T3) in the developmental programming of myosin heavy chain (MHC) isoform expression in neonatal rodent antigravity and locomotor skeletal muscle. The central hypothesis to be tested is that gravity exerts a profound influence on the development and maintenance of slow (type I) MHC expression in antigravity and locomotor muscle, such that in its absence, a significant number of muscle cells up-regulate the expression of fast MHCs due to an increased responsiveness to thyroid hormone. In contrast, the normal expression of the fast IIx and IIb MHCs are developmentally regulated independently of gravity, but require both the presence of an intact nerve and T3 in order for these isoforms to reach full maturation in expression by replacing neonatal MHC isoforms. An additional objective is to determine whether muscle development, in the absence of gravity, creates a deleterious response whereby recovery from exposure to microgravity in the neonatal state, results in an irreversible effect on muscle mass and the pattern of adult myosin isoform expression. To test these hypotheses, both ground control and microgravity exposed neonatal rats (beginning at 2-3 days of age) will be allocated into the following subgroups: normal-control; denervated (DEN); thyroid deficient (TD); and DEN plus TD. The microgravity-exposed neonatal animals (along with the nursing Dams) will be subjected to spaceflight aboard the shuttle (Neurolab mission) for 18-21 days. At recovery (and 3-4 weeks following recovery), flight animals and ground controls will be processed so that key muscles will be obtained to study MHC isoform expression at both the mRNA and protein level of analysis using electrophoretic, immunohistochemical, and in situ hybridization technology. Collectively, these experiments will more clearly delineate the separate and interactive role of those key factors that have been shown to exert a strong influence on muscle development and contractile protein expression.