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.

拟议研究的广泛目标是确定在单一的整个肌肉纤维水平上的细胞和分子事件，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。 具体而言，这些包括1）去神经支配后卫星细胞激活的时间过程和地形，2）在老化和去神经肌肉中与现有肌纤维一起形成新的肌纤维，3）在7个月去神经肌肉中发生的不寻常的核凝集现象，（4）组织中重要基因表达的时程和拓扑图。水平的分子分析似乎在肌纤维对去神经支配和衰老的反应中起重要作用。 McLennan博士的宿主实验室研究了哺乳动物胎儿中肌管的形成，以及组织中肌肉再生的分子方面。 拟议的实验将结合联合收割机博士麦克伦南的分子专业知识与申请人的形态学和实验专业知识，它将汇集麦克伦南博士的经验，在研究产前肌细胞水平与申请人，谁是研究新肌在另一端的寿命。 这项拟议中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恢复能力的方法。