RUI: Investigation of Mechanism of Spermidine Action in Promotion of Neurite Outgrowth

RUI：亚精胺促进神经突生长的作用机制研究

• 批准号: 0550163
• 负责人: Kristen Boeshore
• 金额: $ 13.46万
• 依托单位: Lebanon Valley College
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-08-22 至 2009-01-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0550163&HistoricalAwards=false
• 关键词: RUI; Investigation; Mechanism; Spermidine; Action

Investigation of mechanism of spermidine action in promotion of neurite outgrowthRegions of the peripheral nervous system are capable of extensive spontaneous regeneration following injury. It has recently been found that synthesis of two polyamines, putrescine and spermidine, increases following injury of the superior cervical ganglion (SCG). Furthermore, spermidine has been shown to promote outgrowth of neurites in the PC12 cell model of sympathetic neurons, suggesting a possible involvement in the regenerative process. In the work supported by this proposal, the molecular mechanisms that underlie the ability of spermidine to promote outgrowth will be investigated. Specifically, the ability of spermidine to alter the activation state of members of the Rho family of GTPases will be examined; this family of proteins is involved in cell shape changes. Since regeneration in the central nervous system (CNS) is inhibited, in part, by myelin-associated glycoprotein (MAG), the ability of spermidine to promote neurite outgrowth from PC12 cells grown on this normally inhibitory substrate will be tested. Finally, the involvement of the Rho GTPases in the spontaneous regeneration that occurs following injury of the SCG will be investigated. The nerves exiting the SCG in adult male rats will be transected, and the activation states of the Rho GTPases will subsequently be analyzed. Together, these studies are intended to elucidate the molecular pathway by which spermidine promotes neurite outgrowth in vitro (in the PC12 cells) as well as to uncover a similar function during spontaneous regeneration of the adult rat SCG in vivo. The proposed work will provide educational opportunities for undergraduate students, allowing them to participate in an active research environment beyond the scope of typical classroom or laboratory instruction. Students will be able to address questions within the realm of neurobiology while learning techniques of cell and molecular biology. Such opportunities will further prepare students for research careers and for graduate school.

对促进周围神经系统神经突的产物促进的精子作用机理的调查能够在受伤后能够广泛自发再生。 最近发现，在上宫颈神经节（SCG）损伤后，两种多胺（腐烂和精子）的合成增加。 此外，已经证明精子可以促进交感神经元的PC12细胞模型中神经突的生长，这表明可能参与再生过程。 在该提案支持的工作中，将研究精子促进生长能力的分子机制。 具体而言，将检查精子改变GTPases家族成员的激活状态的能力；该蛋白质家族参与细胞形状的变化。 由于中枢神经系统（CNS）的再生部分受到髓磷脂相关糖蛋白（MAG）的抑制，因此将测试精子促促进精子促进神经突生长的能力。 最后，将研究Rho GTPases参与SCG受伤后发生的自发再生。 将跨成年雄性大鼠退出SCG的神经将被转移，随后将分析Rho GTPases的激活状态。 总之，这些研究旨在阐明精子中促进体外促进神经突生长的分子途径（在PC12细胞中），并在体内自发再生过程中发现了相似的功能。 拟议的工作将为本科生提供教育机会，使他们能够参加典型的课堂或实验室教学范围之外的积极研究环境。 在学习细胞和分子生物学技术的同时，学生将能够在神经生物学领域中解决问题。 这样的机会将进一步为学生准备研究职业和研究生院。