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: 3381092
• 负责人: JEFFREY D WHITE
• 金额: $ 9.93万
• 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/3381092
• 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不可或缺的组成部分 在中枢神经系统（CNS）中。 它们广泛但离散， 分布并促进许多生理学和电生理学 功能。 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 神经肽产生有关神经肽基因表达的信息， 前体蛋白质结构和神经肽的明显异常 在多种中枢神经系统疾病中表达。 蛋白质生化方法有 提供了有关翻译后蛋白水解加工的信息 神经肽激素原。 然而，相对缺乏 有关特定生理作用的信息 中枢神经系统内定义的末端区域中的神经肽。 拟议的 研究将集中于研究神经肽的作用 Y (NPY) 在生理学和解剖学上明确定义的系统中 海马体是全面理解调节的一步 这种神经肽的生物合成和代谢。 首先， 拟议的研究将调查生物合成和翻译后 正常动物和特定动物体内 NPY 的加工 诱导复发性边缘癫痫发作后的时间。 此类癫痫发作有 已被用于证明三种定义的 NPY 基因表达的调节 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。 二、生化过程 响应 NPY 受体的激活而被激活的 对这些神经元的细胞体和神经末梢区域进行了研究 与特定的 NPY 受体激动剂联合使用。 三、可能性 突触蛋白水解会产生额外的、具有生物活性的 NPY- 将研究衍生的肽片段。 当放在一起时， 拟议研究的数据将提供有关以下方面的重要信息： NPY 的加工和生理作用，可能有助于揭示 神经元中激活的保护性细胞机制 病理状况。