CONTROL OF POLARITY IN REGENERATING NEURONS

再生神经元的极性控制

• 批准号: 3478238
• 负责人: GARTH F HALL
• 金额: $ 7.8万
• 依托单位: BOSTON CHILDREN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-02-01 至 1994-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3478238
• 关键词: Agnatha; alternatives to animals in research; axon; calcium; calcium flux; calcium indicator; cellular polarity; chemical stability; colchicine; dendrites; diacylglycerols; dyes; experimental brain lesion; immunocytochemistry; microinjections; microtubules; molecular site; nervous system regeneration; neurofilament; neuronal guidance; okadaic acid; paclitaxel; phosphorylation; protein kinase C; sphingosine

I propose to study the polarity of axonal regeneration in a primitive vertebrate, the sea lamprey, Petromyzon marinus. My goal is to understand how neurons maintain their normal polarity following axotomy; i.e., how they regenerate their axons at the axon stump, by-passing other sites within the cell. The lamprey is ideal for addressing this question, as it permits direct access to and visualization of mature identified neurons in a vertebrate CNS in situ. Furthermore, the site of axotomy of certain identified neurons (ABCs) determines whether axonal regeneration occurs from the axon stump (following axotomy distant from the soma) or from ectopic sites in the dendrites (following axotomy close to the soma). I will therefore compare the effects of close .and distant axotomy on factors that preliminary experiments suggest may be important in maintaining normal polarity (i.e., the distribution and phosphorylation of neurofilaments, the stability of microtubules and the influx of Ca++ at the site of axotomy). The importance of each of these factors in maintaining normal polarity following axotomy will be assessed by (1) comparing post lesion changes in these factors that correlate with the occurrence and distribution of sprouts, and (2) perturbing neurofilament transport and phosphorylation, microtubule stability and the intracellular free Ca++ level with specifically acting drugs, and then examining the response of treated ABCs to axotomy. The results of this work should illuminate the cellular mechanisms that maintain axonal and dendritic identity following injury. They should also be relevant to the important health related problems of CNS axonal regeneration and the loss of aspects of dendritic and axonal identity that occur in Alzheimer's disease.

我建议研究原始的轴突再生的极性 脊椎动物，海七七七空me，彼得罗逊·马里努斯。 我的目标是 了解轴切开术后神经元如何保持其正常极性； 即，它们如何在轴突树桩上再生轴突，通过其他 单元内的站点。 七lamp虫是解决这个问题的理想之选 问题，因为它允许直接访问和可视化成熟 在原位识别脊椎动物中枢神经系统中的神经元。 此外， 某些已识别神经元（ABC）的轴切开术确定轴突是否是否 再生发生在轴突树桩（后轴切开术）远离 soma）或从树突中的异位部位（轴切开后关闭 到索马）。 因此，我将比较近距离和遥远的效果 初步实验表明可能很重要的因素的轴突切开术 保持正常极性（即分布和 神经丝的磷酸化，微管的稳定性和 在轴切开术部位涌入Ca ++）。 这些的重要性 将评估轴切开后保持正常极性的因素 通过（1）比较这些因素的病变变化，这些因素与 芽的发生和分布，以及（2）扰动 神经丝传输和磷酸化，微管稳定性和 具有特定作用药物的细胞内游离CA ++水平，并且 然后检查处理过的ABC对轴切开术的反应。 这项工作的结果应阐明细胞机制 损伤后保持轴突和树突状身份。 他们应该 也与CNS Axonal的重要健康问题有关 再生以及树突状和轴突身份的各个方面的丧失 这发生在阿尔茨海默氏病。