NEUROACTIVE SUBSTANCES, MOTONEURONS, AND ALS

神经活性物质、运动神经元和 ALS

• 批准号: 3404487
• 负责人: NIHAL C DE LANEROLLE
• 金额: $ 12.73万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-02-01 至 1989-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3404487
• 关键词: Macaca; degenerative motor system disease; electron microscopy; histochemistry /cytochemistry; human tissue; immunochemistry; microscopy; motor neurons; neuroanatomy; neuropeptides; ventral column

Neurotransmitter abnormalities have been considered in the probable etiology of ALS. Our conceptual position as to how neuroactive substances (neurotransmitters and neuromodulators) may be involved is that these substances (especially the neuropeptides) in neurons presynaptic to motoneurons may have "trophic" effects on the motoneuron, and selective loss of some of the presynaptic neurochemical systems may be the predisposing factor in the development of ALS. However, little is known about neuroactive substances contained within motoneurons or in neural systems innervating motoneurons. The proposed study principally aims at identifying the neuroactive substances, in particular neuropeptides and other neuromodulatory agents that are associated with spinal motoneurons in the monkey and human. Light microscopic immunohistochemical techniques will be employed to localize a wide range of neuroactive substances in all motoneuron columns of the human and monkey spinal cord. From such studies it will be ascertained if there are any significant differences in the patterns of distribution of neurochemicals in spinal motoneuron groups susceptible to motoneuron degeneration (e.g. Onuf's nucleus and phrenic nucleus) as compared to non-susceptible groups of motoneurons. Electron microscopic immunohistochemical analyses will determine the ultrastructural localization of neuroactive substances in various motoneuron columns, and the relationship of immunoreactive structures to motoneurons. The co-existence of neuroactive substances within terminals will be explored by double labeling immunocytochemical methods. Our conceptual position will be evaluated in part by studying the distribution of neuropeptides and monoamines in spinal cord tissue from deceased ALS patients.

神经递质异常被认为是可能的 ALS的病因。 我们对于神经活性物质 （神经递质和神经调质）可能涉及的是， 突触前神经元中的物质（尤其是神经肽）， 运动神经元可能对运动神经元具有“营养”作用， 一些突触前神经化学系统的丧失可能是 ALS发展中的诱发因素。 然而， 关于运动神经元或神经细胞中所含的神经活性物质 支配运动神经元的系统。 拟议研究的主要目的是 鉴定神经活性物质，特别是神经肽，和 与脊髓运动神经元相关的其他神经调节剂 猴子和人类 光镜免疫组织化学技术 将被用来定位广泛的神经活性物质在所有 人类和猴子脊髓的运动神经元柱。 从这些研究 将确定是否存在任何显著差异， 脊髓运动神经元群中神经化学物质的分布模式 易受运动神经元变性影响（例如Onuf核和膈神经 与运动神经元的非易感组相比。 电子 显微免疫组织化学分析将确定超微结构 神经活性物质在各种运动神经元柱中的定位，以及 免疫反应结构与运动神经元的关系。 的 神经活性物质在终端内的共存将通过以下方式进行探索： 免疫细胞化学双标法。 我们的概念立场将 部分通过研究神经肽的分布进行评估， 脊髓组织中的单胺。