NEUROACTIVE SUBSTANCES, MOTONEURONS, AND ALS

神经递质异常被认为是可能的 肌萎缩侧索硬化症的病因。我们关于神经活性物质如何 (神经递质和神经调节剂)可能参与的是这些 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，并具有选择性 一些突触前神经化学系统的丧失可能是 肌萎缩侧索硬化症发病的易感因素然而，人们对此知之甚少 关于运动神经元或神经细胞中含有的神经活性物质 支配运动神经元的系统。建议的研究主要目的是 识别神经活性物质，特别是神经肽和 其他与脊髓运动神经元相关的神经调节剂 猴子和人类。光镜免疫组织化学技术 将被用来在所有的 人和猴子脊髓的运动神经元柱。从这些研究中 将确定是否有任何显著的差异在 脊髓运动神经元群内神经化学物质的分布模式 易患运动神经元变性(如Onuf核和膈 核团)，与不敏感的运动神经元群相比。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中的定位，以及 免疫反应结构与运动神经元的关系。这个 终端内神经活性物质的共存将通过 免疫细胞化学双标记方法。我们的概念定位将是 部分通过研究神经肽的分布和 ALS患者脊髓组织中的单胺类物质。

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.