SCHWANN CELLS IN AGING MUSCLE

肌肉老化中的雪旺细胞

• 批准号: 2632602
• 负责人: WESLEY J THOMPSON
• 金额: $ 7.55万
• 依托单位: UNIVERSITY OF TEXAS AT AUSTIN
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-05-01 至 2000-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2632602
• 关键词: Schwann cells; age difference; aging; botulinum toxins; cell cell interaction; cell death; cell growth regulation; denervation; immunocytochemistry; laboratory rat; male castration; morphology; nervous system regeneration; neuromuscular junction; testosterone

An examination of glial cells at aging neuromuscular junctions is proposed. One of the hallmarks of aging in humans is a loss of muscle fibers and, consequently, a loss of muscle strength. The loss of muscle fibers appears to be due to a failure of aging fibers to successfully regenerate following mechanical damage. Failure of muscle regeneration has been attributed to a failure of the regenerating fibers to become innervated. The glial or Schwann cells that cover the neuromuscular junction have recently been shown to play a major role in the repair and maintenance of neuromuscular junctions. These cells induce and guide nerve growth through the processes they extend in response to perturbations in muscle innervation. Moreover, activation of the Schwann cells at neuromuscular junctions can dramatically perturb the synaptic connection. Therefore it appears that age-related changes in Schwann cells could underlie some of the changes in muscle innervation. To examine this possibility, it is proposed to determine how the number and morphology of terminal Schwann cells is altered in aging rat muscle. Preliminary results suggest that as junctions age they gain Schwann cells. However, the junctions are also growing in size and it may be this increase in size rather than aging per se that leads to addition of Schwann cells. To examine this we will shrink and expand the size of fibers (and thus the junctions made upon them) in androgen-sensitive muscles in male rats by castration and testosterone administration. When muscles of the same age, but different size are compared, it should be possible to determine whether age or size determines the number of Schwann cells. We will also examine the responsiveness of Schwann cells at aging junctions to denervation, partial denervation, and muscle paralysis. These are conditions which in young adult animals lead to the growth of Schwann cell processes that promote nerve growth and repair of innervation. We will determine whether there are any deficiencies in the growth of Schwann cells in aging rat muscle. The results of this pilot study should provide evidence concerning the involvement of synaptic glial cells in the aging process.

检查衰老神经肌肉连接处的神经胶质细胞是 建议的。 人类衰老的标志之一是失去肌肉 纤维，因此是肌肉力量的损失。 肌肉的丧失 纤维似乎是由于衰老纤维无法成功的失败 机械损坏后再生。肌肉再生的失败 归因于再生纤维的失败 支配。 覆盖神经肌肉的神经胶质细胞 最近已显示交界处在维修中起主要作用 维护神经肌肉连接。 这些细胞诱导和引导 通过它们扩展为响应的过程，神经生长 肌肉神经的扰动。 此外，激活 神经肌肉连接处的Schwann细胞会极大地扰动 突触连接。 因此，似乎与年龄相关的变化 雪旺细胞可能是肌肉神经支配的某些变化的基础。 为了检查这种可能性，建议确定数量 在衰老的大鼠肌肉中，末端雪旺细胞的形态发生了变化。 初步结果表明，随着连接年龄的增长，它们会获得Schwann 细胞。 但是，交界处的大小也在增长，可能是 大小的增加而不是衰老，这会导致添加 Schwann细胞。 为了检查这一点，我们将缩小并扩大大小 在雄激素敏感的 通过cast割和睾丸激素给药中雄性大鼠的肌肉。 当相同年龄但比较不同大小的肌肉时，应该 可以确定年龄或大小是否确定 Schwann细胞。 我们还将检查Schwann细胞的响应能力 在衰老的连接处与改造，部分改造和肌肉 麻痹。 这些条件在年轻的成年动物中导致 促进神经生长和 神经修复。 我们将确定是否有 老化大鼠肌肉中雪旺细胞生长的缺乏。 这 这项试验研究的结果应提供有关 突触神经胶质细胞参与衰老过程。