NEUROPEPTIDE BIOSYNTHESIS AND METABOLISM IN THE CNS

中枢神经系统中的神经肽生物合成和代谢

• 批准号: 3381089
• 负责人: JEFFREY D WHITE
• 金额: $ 9.87万
• 依托单位: STATE UNIVERSITY NEW YORK STONY BROOK
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-09-30 至 1996-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3381089
• 关键词: brain metabolism; dentate gyrus; experimental brain lesion; gene expression; granule; high performance liquid chromatography; hippocampus; laboratory rat; messenger RNA; neuronal transport; neuropeptide Y; neuropeptide receptor; neurotransmitter biosynthesis; neurotransmitter metabolism; partial seizure; posttranslational modifications; pyramidal cells; radiotracer; second messengers

Neuropeptides are recognized as integral components of information transfer in the central nervous system (CNS). They are widely, but discretely, distributed and subserve a number of physiological and electrophysiological functions. Recent progress in molecular biology has allowed the cloning of the cDNAs and genes encoding the precursor proteins for a variety of neuropeptides yielding information on neuropeptide gene expression, precursor protein structure, and apparent abnormalities in neuropeptide expression in several CNS disorders. Protein biochemical methods have provided information about the post-translational proteolytic processing of neuropeptide prohormones. There is, however, a relative paucity of information regarding the physiological roles subserved by specific neuropeptides in defined terminal fields within the CNS. The proposed research will concentrate on investigations into the role of neuropeptide Y (NPY) in the physiologically and anatomically well-defined system of the hippocampus as one step toward a complete understanding of the regulation of the biosynthesis and metabolism of this neuropeptide. First, the proposed studies will investigate the biosynthesis and post-translational processing of NPY in vivo in normal animals and in animals at specific times following induction of recurrent limbic seizures. Such seizures have been used to demonstrate modulation of NPY gene expression in three defined neuronal populations within the hippocampus: hilar neurons, dentate gyrus granule cells and CA1 pyramidal cells. Second, the biochemical processes that are activated in response to activation of NPY receptors will be investigated in the cell body and nerve terminal fields of these neurons in combination with specific NPY receptor agonist. Third, the possibility that synaptic proteolysis results in additional, biologically active NPY- derived peptide fragments will be investigated. When taken together, the data from the proposed studies will provide essential information regarding the processing and physiological actions of NPY and may shed light on protective cellular mechanisms which are activated in neurons in pathological conditions.

神经肽被认为是信息传递的组成部分 中枢神经系统（CNS）。 他们广泛，但离散， 分布和维护许多生理和电生理 功能协调发展的 分子生物学的最新进展使得克隆 编码多种前体蛋白的cDNA和基因， 产生神经肽基因表达信息的神经肽， 前体蛋白质结构和神经肽的明显异常 在几种CNS疾病中表达。 蛋白质生化方法有 提供了关于蛋白质翻译后蛋白水解过程的信息， 神经肽激素原 然而，相对而言， 关于特定的生理作用的信息 在CNS内的定义的终端领域的神经肽。 拟议 研究将集中于神经肽的作用 Y（NPY）在生理学和解剖学上明确定义的系统中， 海马体作为一个完整的了解调控的一步 这种神经肽的生物合成和代谢。 一是 拟议的研究将调查生物合成和翻译后 在正常动物和特定条件下的动物中， 诱导复发性边缘系统癫痫发作后的时间。 这种癫痫发作有 已经被用来证明在三个定义的神经肽Y基因表达的调制 海马内的神经元群：门神经元、齿状回 颗粒细胞和CA1锥体细胞。 第二，生物化学过程 在神经肽Y受体激活后， 在这些神经元的细胞体和神经末梢领域进行了研究， 与特异性NPY受体激动剂组合。 第三，可能性 突触蛋白水解导致额外的生物活性NPY， 将研究衍生的肽片段。 当我们一起考虑时， 来自拟议研究的数据将提供以下方面的基本信息 神经肽Y的加工和生理作用，并可能揭示 保护性细胞机制在神经元中被激活， 病理条件。