AGING AND NEUROMUSCULAR DEGENERATION AND REGENERATION

衰老与神经肌肉退化和再生

• 批准号: 3116976
• 负责人: DEBORAH W VAUGHAN
• 金额: $ 8.78万
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-09-30 至 1989-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3116976
• 关键词: aging; animal old age; axon; computer data analysis; denervation; electron microscopy; glia; histochemistry /cytochemistry; innervation; mature animal; nervous system regeneration; neural degeneration; neuromuscular function; peripheral nervous system disorders; trauma

The responses of motor neurons and muscles to axon injury have been well characterized in newborn through young adult animals, but they have not been examined in aged animals. In view of the anabolic nature of the axon reaction, increasing evidence that advancing age alters neuronal energy metabolism, and the independent effects of advancing age on muscle fibers, it is the aim of this research to determine whether the patterns of degenerative and regenerative changes in neurons and target muscles are the same after axon injury in young adult and middle-aged animals. This question is important for better understanding of age-related differences in the process of peripheral nerve regeneration and muscle reinnervation in the aging human population following axon trauma. Furthermore, it shall provide spacial, temporal, and metabolic frames of reference for subsequent studies conducted on any one part of the neuromuscular system, at any age. The proposed study examines several regions of a specific neuromuscular system and compares the nature and significance of axotomy-induced morphological and enzymatic changes in young adult (3-month old) and middle-aged (15-month old) rats. The model to be used is the motor neuron of the facial nucleus, and two forms of axon injury of differing severity are proposed. Thus at the site where the facial nerve exits the skull at the stylomastoid foramen, this nerve will be either crushed and reinnervation allowed to occur, or ligated and a segment excised to prevent reinnervation. After a series of postoperative survival times, which range between 2 days and 4 months after injury, observations will be made on the following regions of the motor system: the neuronal cell bodies and their supporting neuroglial cells in the facial nucleus, the axons proximal to the injury in the facial nerve as it exits the brain stem, the distal axons in the buccal branch of the nerve beyond the site of the injury, the motor end plates terminating on the nasolabialis muscles, and the deafferented muscle fibers of the nasolabialis muscle. From observations, as well as computer-assisted stereological analysis of light, electron microscope and enzyme histochemical preparations of these regions at each of the postoperative times, it will be possible to identify differences in both the intensity and the temporal patterns of the response of the entire system to axon injury as influenced by both the age of the animal and the severity of the axon injury.

运动神经元和肌肉对轴突损伤的反应良好。 以刚出生到成年的动物为特征，但它们没有 在老年动物身上进行了检测。鉴于轴突的合成代谢特性 反应，越来越多的证据表明年龄增长会改变神经元能量 代谢，以及年龄增长对肌肉纤维的独立影响， 这项研究的目的是确定是否存在 神经元和靶肌肉的退行性和再生性变化是 幼年和中年动物轴突损伤后也是如此。这 问题对于更好地理解与年龄有关的差异是重要的 在周围神经再生和肌肉再支配的过程中 轴突损伤后的老龄化人口。此外，它还应 为后续工作提供空间、时间和代谢参照系 在任何年龄对神经肌肉系统的任何一个部分进行的研究。 这项拟议的研究检查了特定神经肌肉的几个区域 系统比较了轴突切断术的性质和意义 青年(3月龄)和幼年(3月龄)的形态和酶的变化 中年(15月龄)大鼠。要使用的模型是运动神经元 以及两种不同严重程度的轴突损伤 都被提出了。因此，在面神经出颅骨的部位 茎乳突孔，这条神经要么被挤压，要么 允许发生再神经支配，或结扎和切除节段以防止 神经再支配。经过一系列的术后生存时间，哪些范围 在受伤后2天至4个月期间，将对 运动系统的以下区域：神经元胞体及其 支持面神经核内的神经胶质细胞，近端轴突 面神经离开脑干，即远端轴突时的损伤 在损伤部位以外的神经颊支，运动 终板终止于鼻唇肌和传出神经 鼻唇肌的肌纤维。从观察到的，以及 计算机辅助光学、电子显微镜和计算机辅助体视学分析 这些区域的酶组织化学准备 术后的时间，将有可能确定两者的差异 整体反应的强度和时间模式 动物年龄和年龄对轴突损伤系统的影响 轴突损伤的严重程度。