AGE, AXON INJURY AND MOTOR NEURON SYNAPTOLOGY

年龄、轴突损伤和运动神经元突触

• 批准号: 3121806
• 负责人: DEBORAH W VAUGHAN
• 金额: $ 14.61万
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-06-01 至 1994-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3121806
• 关键词: aging; animal age group; axon; facial nerve; immunocytochemistry; immunoelectron microscopy; injury; laboratory rat; motor neurons; nervous system regeneration; neural degeneration; synapses

When the axon of a motor neuron is injured, the neuron loses much of its central afferent connectionns. These central changes are reversed when the axons restore appropriate peripheral contacts. This proposal aims to examine the changing synaptic relationships of injured facial motor neurons following crush injury of the facial nerve in young (3 month) and middle aged (15 month) rats. The model for this analysis is ideal because the facial nucleus is a homogeneous population of motor neurons, its afferent innervation is well characterized, and it loses no neurons with advancing age. Our preliminary studies suggest that recovery of central afferent connections may be incomplete in older animals following peripheral reinnervation. The facial motor nucleus will be examined using morphometry and electron microscope immunocytochemistry to determine the identity of terminals showing GABA-like, serotonin-like and noradrenalin-like immunoreactivity. Standard procedures of fine structure morphometry (including reconstruction from serial thin sections) will establish a "catalog" of all morphological types of axon boutons in the normal facial nucleus. Following axon crush the response of the identified terminals will be characterized as to their fate and recovery, as will the response of the neurons and neuroglial cells. In addition, autoradiographic analysis will determine the dynamics of loss and recovery of postsynaptic GABA-A, serotonin IA and 2, and Beta- adrenoceptor ligand binding. Receptor dynamics will be correlated with binding to serotonin and noradrenalin uptake sites and presynaptic receptors. These studies will establish a bridge between the results of anatomical, immunocytochemical and pharmacological approaches to the investigation of the effects of advancing age on motor neuron response to injury. Given the crucial role of these synaptic connections and receptors in neuronal excitability and calcium mobilization it is important to understand how advancing age compromises the ability of neurons to recover from peripheral nerve injury. Such understanding is important to the development of therapeutic intervention designed to improve nerve regeneration.

当运动神经元的轴突受损时，神经元失去其大部分的功能。 中枢传入连接 当这些核心变化发生时， 轴突恢复适当的外周接触。 这项建议旨在 来检查受损的面部运动神经突触关系的变化， 年轻人（3个月）面神经挤压伤后的神经元 和中年（15个月）大鼠。 该分析的模型是理想的 因为面神经核是运动神经元的同质群体， 它的传入神经支配很好地表征了， 随着年龄的增长。 我们的初步研究表明， 在老年动物中，中枢传入连接可能不完整 周围神经再支配后 面神经运动核将采用形态计量学和电子显微镜检查 显微镜免疫细胞化学以确定终末的身份 表现出GABA样、肾上腺素样和去甲肾上腺素样 免疫反应性。 精细结构形态测量标准程序 （包括从连续薄切片重建）将建立一个 “目录”的所有形态类型的轴突终扣在正常的 面神经核 轴突挤压后， 终端将被描述为它们的命运和恢复， 神经元和神经胶质细胞的反应。 此外，本发明还提供了一种方法， 放射自显影分析将确定损失的动力学， 突触后GABA-A、5-羟色胺IA和2以及β- 肾上腺素受体配体结合 受体动力学将与 与5-羟色胺和去甲肾上腺素摄取位点结合， 受体。 这些研究将在以下结果之间建立桥梁： 从解剖学、免疫细胞化学和药理学的角度 增龄对运动神经元反应影响的研究 受伤。 考虑到这些突触连接和受体在 神经元兴奋性和钙动员，重要的是， 了解年龄增长如何损害神经元的能力， 从周围神经损伤中恢复。 这样的理解很重要 旨在改善神经系统的治疗干预的发展 再生