ULTRASTRUCTURE AND FUNCTION OF NERVE AND MUSCLE

神经和肌肉的超微结构和功能

• 批准号: 3116887
• 负责人: YASUKO NAKAJIMA
• 金额: $ 18.18万
• 依托单位: UNIVERSITY OF ILLINOIS AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-03-01 至 1996-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3116887
• 关键词: Alzheimer's disease; electron microscopy; electrophysiology; guanine nucleotide binding protein; histochemistry /cytochemistry; laboratory mouse; laboratory rat; locus coeruleus; neural information processing; neuroanatomy; neurons; neuropeptides; neurotensin; second messengers; somatostatin; substance P; synapses; tissue /cell culture

The objective of this proposal is to understand the cellular and subcellular mechanisms by which various neuropeptides modulate the activity of brain neurons. Particularly, these studies attempt to elucidate the function and structure of brain neurons that are correlated with Alzheimer's disease. It was for this purpose that the principal investigator (P.I.) developed a unique method of culturing cholinergic neurons from the basal forebrain nuclei including the nucleus basalis as well as the noradrenergic neurons from the locus careless. Neurons in these nuclei have been shown to degenerate in Alzheimer's disease. Cultured cholinergic neurons and noradrenergic neurons were identified using immunocytochemical and histochemical methods. The P.I. plans to study the signal transduction process involved in the effects of neuropeptides on these primary cultures with particular emphasis on the mechanism by which second messengers modulate potassium channels. There are three major projects: The first project deals with the modulation of the inwardly rectifying K- channels by substance P and somatostatin in nucleus basalis and locus careless neurons. The P.I.'s previous work has demonstrated that substance P excites neurons by suppressing an inwardly rectifying K-conductance, whereas somatostatin inhibits them by inducing a similar conductance. This work will be extended at the single channel level to include a detailed analysis of the properties of these potassium channels. The second project is to identify the second messengers. The P.I. has found that two different GTP-binding proteins seem to be the second messengers for the substance P- and somatostatin-induced modulations of potassium conductance. In this project,the P.I. proposes to examine the role that arachidonic acid metabolites play in somatostatin- and substance P-induced modulation of potassium channels. The third project is to study the ionic and second messenger mechanisms involved in the effects of galanin and neurotensin on cultured nucleus basalis and locus careless neurons using the whole-cell clamp and single- channel recording. Preliminary results from the pilot study suggest that galanin inhibits locus careless neurons, whereas both galanin and neurotensin excite nucleus basalis neurons.

这项建议的目标是了解细胞和 不同神经肽调节活性的亚细胞机制 大脑神经元的。特别是，这些研究试图阐明 脑神经元的功能和结构与之相关 阿尔茨海默氏症。正是出于这个目的，校长 调查员(私家侦探)开发了一种独特的胆碱能细胞培养方法 来自包括基底核在内的前脑基底核团的神经元 以及来自疏忽部位的去甲肾上腺素能神经元。神经元中的 这些核团已被证明在阿尔茨海默病中退化。 鉴定培养的胆碱能神经元和去甲肾上腺素能神经元 采用免疫细胞化学和组织化学方法。私家侦探计划 研究信号转导过程中参与的影响 这些原代培养物上的神经肽，特别强调 第二信使调节钾通道的机制。那里 有三个主要项目： 第一个项目涉及对内向整流K-的调制。 P物质和生长抑素在基底核和基底核的通道 粗心大意的神经元。私家侦探S之前的工作就证明了这一点 P通过抑制向内整流的钾电导来兴奋神经元， 而生长抑素通过诱导类似的电导来抑制它们。这 工作将扩展到单一渠道级别，以包括详细的 对这些钾通道的特性进行分析。 第二个项目是确定第二个信使。私家侦探已经 发现两种不同的GTP结合蛋白似乎是第二种 P物质和生长抑素诱导的血管紧张素转运蛋白 钾电导。在这个项目中，私家侦探建议检查 花生四烯酸代谢产物在生长抑素及其物质中的作用 磷诱导钾通道的调制。 第三个项目是研究离子信使和第二信使机制。 甘丙肽和神经降压素对培养细胞核的影响 用全细胞钳和单细胞钳记录基底区和斑点区粗大神经元 频道录制。初步研究结果表明， 甘丙素抑制粗大神经元，而甘丙素和甘丙素 神经降压素兴奋基底核神经元。