SINGLE FIBER ANALYSIS OF DENERVATED AND AGING MUSCLE

去神经支配和老化肌肉的单纤维分析

• 批准号: 2863149
• 负责人: BRUCE M CARLSON
• 金额: $ 3.48万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-04-16 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/2863149
• 关键词: aging; apoptosis; cell proliferation; denervation; gene expression; immunocytochemistry; innervation; laboratory rat; motor neurons; muscle satellite cell; myofibrils; myogenesis; myotubes; neuroeffector; neuromuscular junction; regeneration; sciatic nerve

The broad goal of the proposed research is to determine at the single whole muscle fiber level cellular and molecular events that underlie reactions that have been observed in both aging and long-term denervated muscle. Specifically, these include 1) the time course and topography of satellite cell activation after denervation, 2) the formation of new muscle fibers alongside existing ones in both aging and denervated muscle, 3) an unusual nuclear clumping phenomenon that occurs in 7-month denervated muscle, and 4) the time course and topography of expression of important genes that from tissue-level molecular analysis appear to play an important role in the reactions of muscle fibers to both denervation and aging. The host laboratory of Dr. McLennan has studied myotube formation in the mammalian fetus, as well as molecular aspects of muscle regeneration in tissues. The proposed experiments will combine Dr. McLennan's molecular expertise with the applicant's morphological and experimental expertise, and it will bring together Dr. McLennan's experience in studying prenatal myogenesis at the cellular level with that of the applicant, who is studying neomyogenesis at the other end of the life span. The proposed research is part of a project designed to devise ways of enhancing the restorative ability of aging and denervated muscles.

拟议研究的总体目标是在单个完整肌纤维水平上确定细胞和分子事件，这些事件是在衰老和长期失神经肌肉中观察到的反应的基础。 具体来说，这些包括 1) 去神经后卫星细胞激活的时间过程和地形，2) 新肌肉纤维与衰老和去神经肌肉中现有的肌肉纤维一起形成，3) 7 个月去神经肌肉中发生的不寻常的核聚集现象，以及 4) 重要基因表达的时间过程和地形，从组织水平分子分析来看，这些基因似乎在肌肉反应中发挥着重要作用 纤维去神经支配和衰老。 麦克伦南博士的所在实验室研究了哺乳动物胎儿的肌管形成，以及组织中肌肉再生的分子方面。 拟议的实验将把麦克伦南博士的分子专业知识与申请人的形态学和实验专业知识结合起来，并将麦克伦南博士在细胞水平上研究产前肌发生的经验与申请人正在研究生命另一端的新生肌发生的经验结合起来。 拟议的研究是一个项目的一部分，该项目旨在设计增强衰老和失神经肌肉的恢复能力的方法。