SLOW AXONAL TRANSPORT IN CNS DEVELOPMENT

已知通过缓慢轴突运输的细胞骨架蛋白的递送， 在轴突生长中起着重要作用，但我们目前的信息表明， 哺乳动物中枢神经系统轴突发育过程的细节是极其复杂的。 有限公司 此外，我们目前几乎一无所知， 轴突细胞骨架和细胞基质蛋白合成和转运 在哺乳动物中枢神经系统轴突对损伤的反应中。 理想的CNS系统 仓鼠的皮质脊髓束是用来研究这些问题的。 皮质脊髓轴突起源于运动皮层，支配所有 脊髓节段，主要在出生后发育。 但是，在未成熟的动物中，这些轴突表现出显著的 可塑性，并已被证明在受伤后进行一些再生。 因此，可以在初始发育期间检查该系统的轴突， 在一段时间内，当他们保持再生能力， 成熟 拟议的研究将首先审查 正常发育过程中发生的缓慢轴突运输参数 以及这些轴突的成熟，然后确定损伤如何影响这些轴突， 参数 轴突慢成分转运蛋白 运输，SCa和SCb）（包括肌动蛋白，微管蛋白，神经丝蛋白， 微管相关蛋白，肌动蛋白相关蛋白，以及一些 其它蛋白质）将通过注射放射性标记的 氨基酸进入运动皮层，并在它们通过 慢轴突运输。 将使用凝胶电泳和荧光照相术 生物化学表征轴突细胞骨架的变化， 细胞骨架和相关蛋白转运速率的变化 在发展过程中。 轴突细胞骨架蛋白的异质性， 将检测主要缓慢转运蛋白的定量变化 在发育和受伤后。 通过仔细定义， 定量方式的详细变化，在生化和动力学 的轴突细胞骨架在中枢神经系统轴突，重要的进展，我们在 了解影响再生能力的机制 神经元将被制造出来。

The delivery of cytoskeletal proteins by slow axonal transport is known to have an essential role in axonal growth but our present information on the details of this process in developing CNS axons in mammals is extremely limited. Additionally, we presently know almost nothing about the synthesis and transport of axonal cytoskeletal and cytomatrix proteins during the response to injury in mammalian CNS axons. An ideal CNS system for studying these issues is the corticospinal tract of the hamster. Hamster corticospinal axons arise from the motor cortex, innervate all segments of the spinal cord, and develop predominantly postnatally. Futhermore, in the immature animal, these axons exhibit remarkable plasticity, and have been shown to undergo some regrowth after injury. Thus, axons of this system can be examined during initial development, during a period when they maintain a capacity for regrowth, and in maturity. The proposed studies will first examine changes in the parameters of slow axonal transport that occur during normal development and maturation of these axons, and then determine how injury affects these parameters. Proteins transported with the slow components of axonal transport, SCa and SCb) (including actin, tubulin, neurofilament proteins, microtubule-associated proteins, actin-associated proteins, and a number of other proteins) will be selectively labelled by injecting radiolabelled amino acids into the motor cortex and harvested after they enter axons via slow axonal transport. Gel electrophoresis and fluorography will be used to biochemically characterize changes in the axonal cytoskeleton and assess changes in the rate of transport of cytoskeletal and associated proteins during development. Heterogeneity of axonal cytoskeletal proteins and quantitative changes in major slowly transported proteins will be examined during development and after injury. By defining in a careful and quantitative manner the detailed changes in the biochemistry and dynamics of the axonal cytoskeleton in CNS axons, important advances in our understanding of the mechanisms which influence the regenerative capacity of the neuron will be made.