NEURAL-THYROID INTERACTION ON ISOMYOSIN EXPRESSION

描述：(申请者摘要)这个项目的目标是 检查重力、神经支配和甲状腺的相互作用 肌球蛋白重链发育规划中的激素(T3) (MHC)亚型在新生啮齿动物反重力和运动中的表达 骨骼肌。需要检验的中心假设是重力 对慢工的发展和维护产生了深远的影响 (I型)MHC在反重力和运动肌中的表达，从而 在没有它的情况下，相当数量的肌肉细胞上调 甲状腺反应性增强所致的快速MHC的表达 荷尔蒙。相反，FAST IIx和IIb的正常表达 MHC在发育过程中独立于重力调节，但需要 存在完整的神经和T3以形成这些异构体 通过替换新生儿MHC达到表达的完全成熟 异构体。另一个目标是确定肌肉是否 发展，在没有重力的情况下，会产生有害的反应 从而在新生儿状态下从微重力环境中恢复， 结果对肌肉质量和成人模式产生不可逆转的影响 肌球蛋白亚型的表达。为了检验这些假说，两种说法都 对照组和微重力暴露的新生大鼠(从2-3天开始 年龄)将被分成以下亚组：正常对照组； 失神经(DEN)；甲状腺功能不全(TD)；DEN+TD。这个 暴露在微重力下的新生动物(以及哺乳堤坝)将 在航天飞机上接受太空飞行(神经实验室任务) 18-21天。康复时(康复后3-4周)，飞行 动物和地面控制将被处理，以便关键肌肉将 以研究MHC亚型在mRNA和蛋白质中的表达 使用电泳法、免疫组织化学法和 原位杂交技术。总的来说，这些实验将会有更多 清楚地描述这些关键因素的单独和交互作用 已被证明对肌肉发育有很强的影响 和收缩蛋白的表达。

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.