NEUROPEPTIDE BIOSYNTHESIS AND METABOLISM IN THE CNS

神经肽被认为是信息传递的组成部分 在中枢神经系统(CNS)。它们是广泛的，但也是分散的， 分布和辅助多个生理和电生理 功能。分子生物学的最新进展使克隆 编码多种病毒前体蛋白的cDNA和基因 神经肽产生关于神经肽基因表达的信息， 前体蛋白结构与神经肽的明显异常 在几种中枢神经系统疾病中的表达。蛋白质生化方法有 提供了有关翻译后蛋白质分解处理的信息 神经肽原激素。然而，有一个相对稀缺的 关于特定角色所替代的生理角色的信息 中枢神经系统内定义的终末区域中的神经肽。建议数 研究将集中在神经肽的作用研究上。 Y(NPY)在生理和解剖学上定义明确的 海马体作为通向完全理解调节的一步 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 神经肽Y在正常动物体内和在特定动物体内的处理 诱发复发性边缘惊厥后的次数。这样的癫痫发作已经 已经被用来证明NPY基因的表达在三个定义的 海马区神经元亚群：肺门神经元、齿状回 颗粒细胞和CA1锥体细胞。第二，生化过程 因NPY受体的激活而被激活的基因将 对这些神经元的胞体和神经末梢区域进行了研究 与特异性NPY受体激动剂联合使用。第三，有可能 突触蛋白分解导致额外的、具有生物学活性的NPY- 将对衍生的多肽片段进行研究。当综合起来时， 拟议研究的数据将提供有关以下方面的重要信息 NPY的加工和生理作用及其可能的启示 在神经元中激活的保护性细胞机制 病理情况。

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.