Modulation of Sensory Transmission by Virally Delivered Genes

病毒传递基因对感觉传递的调节

• 批准号: 9728736
• 负责人: Steven Wilson
• 金额: $ 30.97万
• 依托单位: University of South Carolina at Columbia
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-07-01 至 2002-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=9728736&HistoricalAwards=false
• 关键词: Modulation; Sensory; Transmission; Virally; Delivered

The somatic sensory system carries information on touch, temperature and pain to the brain. Nerve cells innervating the skin called 'first-order' neurons send signals to the spinal cord segments, where they make functional connections called synapses to neurons that carry information up and down the spinal column. Biochemical compounds called neurotransmitters are released by the first-order cells to activate or inhibit these target 'second- order' cells, and an important class of these signaling molecules is known as peptides. This project addresses the role of the peptides enkephalin, neuropeptide Y (NPY), and calcitonin-gene related peptide (CGRP) in this neurotransmission. Particular genes or anti-sense constructs will be delivered by a novel methodology utilizing modified viruses, to increase or decrease the production of these peptides in the first-order sensory neurons. Molecular analysis of gene expression, a behavioral assay for sensation, and pharmacological manipulation will determine how the peptides act, and what receptor molecules on the cell surface membranes are responsible for their action. Results are expected to clarify how enkephalins and NPY inhibit sensory transmission, while CGRP facilitates it. This project will have impact beyond simply somatosensory transmission, because it will clarify mechanisms of action for particular neurotransmitters used in other parts of the brain, and the gene-delivery methods to be perfected here will provide a powerful tool to study the roles of other molecular components in neuronal function.

躯体感觉系统将触觉、温度和疼痛的信息传送到大脑。 支配皮肤的神经细胞被称为“一级”神经元，它们将信号发送到脊髓节段，在那里它们与神经元建立功能性连接，称为突触，这些神经元将信息传递到脊柱上下。 被称为神经递质的生物化学化合物由一级细胞释放以激活或抑制这些目标“二级”细胞，并且这些信号分子中的一个重要类别被称为肽。 本计画探讨脑啡肽、神经肽Y（NPY）及降钙素基因相关肽（CGRP）在此神经传递中的作用。 特定的基因或反义构建体将通过利用修饰的病毒的新方法递送，以增加或减少这些肽在一级感觉神经元中的产生。 基因表达的分子分析、感觉的行为测定和药理学操作将确定肽如何起作用，以及细胞表面膜上的哪些受体分子负责它们的作用。 结果有望澄清脑啡肽和NPY如何抑制感觉传递，而CGRP促进它。 该项目的影响将超越简单的躯体感觉传递，因为它将阐明用于大脑其他部位的特定神经递质的作用机制，并且在此完善的基因传递方法将为研究其他分子成分在神经元功能中的作用提供强大的工具。