AGING AND NEUROMUSCULAR DEGENERATION AND REGENERATION

衰老与神经肌肉退化和再生

• 批准号: 3116979
• 负责人: DEBORAH W VAUGHAN
• 金额: $ 9.89万
• 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/3116979
• 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 在新生儿到年轻的成年动物的特点，但他们没有 在老年动物中进行了检查。 鉴于轴突的合成代谢特性 越来越多的证据表明，年龄的增长会改变神经元的能量 新陈代谢，以及年龄增长对肌纤维的独立影响， 这项研究的目的是确定是否有模式的 神经元和靶肌肉的退行性和再生性变化是 在年轻成年和中年动物中轴突损伤后也是如此。 这 这个问题对于更好地理解与年龄相关的差异很重要 在周围神经再生和肌肉神经再支配的过程中， 轴突损伤后的老龄人口。 此外，它应 提供空间、时间和新陈代谢的参考框架， 在任何年龄对神经肌肉系统的任何一部分进行的研究。 这项拟议中的研究检查了一个特定的神经肌肉的几个区域， 系统，并比较轴突切开术诱导的性质和意义 年轻成人（3个月大）的形态学和酶变化， 中年（15个月大）大鼠。 所使用的模型是运动神经元 的面神经核，和两种形式的不同严重程度的轴突损伤 被提议。 因此，在面部神经离开颅骨的部位， 茎乳孔，这条神经要么会被压碎， 允许发生神经再支配，或结扎并切除一段以防止 神经再生 经过一系列的术后生存时间， 受伤后2天至4个月，将对 运动系统的以下区域：神经元细胞体及其 支持面神经核中的神经胶质细胞， 面神经从脑干出来时受到的损伤， 在超出损伤部位的神经的颊分支中， 终板终止于鼻唇肌， 鼻唇肌的肌纤维。 从观察，以及 计算机辅助光、电子显微镜和 酶组织化学制剂的这些区域在每个 术后时间，将有可能确定两者的差异 整个系统的反应强度和时间模式 系统轴突损伤的影响，受年龄的动物和 轴突损伤的严重程度。