SLOW AXONAL TRANSPORT IN CNS DEVELOPMENT

众所周知，通过缓慢的轴突运输运送细胞骨架蛋白 在轴突生长中有重要作用，但我们目前关于轴突生长的信息 哺乳动物中枢神经系统轴突发育的这个过程的细节是非常详细的 有限的。此外，我们目前几乎不知道关于 轴突细胞骨架和细胞基质蛋白的合成和转运 在哺乳动物中枢神经系统轴突对损伤的反应中。一种理想的中枢神经系统 用于研究这些问题的是仓鼠的皮质脊髓束。 仓鼠皮质脊髓轴突起源于运动皮质，支配所有 脊髓的节段，并主要在出生后发育。 此外，在未成熟的动物中，这些轴突表现出显著的 可塑性，并已被证明经历了一些损伤后的再生长。 因此，可以在最初的发育过程中检查该系统的轴突， 在它们保持再生能力的时期，以及在 成熟。拟议的研究将首先研究 正常发育过程中轴突运输缓慢的参数 以及这些轴突的成熟，然后确定损伤如何影响这些 参数。与轴突慢成分一起运输的蛋白质 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、肌动蛋白相关蛋白和一些 其他蛋白质)将通过注射放射性标记来选择性地标记 氨基酸进入运动皮质，并在进入轴突后通过 轴突运输缓慢。将使用凝胶电泳法和荧光法 以生化方法描述轴突细胞骨架的变化，并评估 细胞骨架及相关蛋白质转运速率的变化 在开发过程中。轴突细胞骨架蛋白的异质性和 主要运输缓慢的蛋白质的数量变化将被检测。 在发育过程中和受伤后。通过仔细地定义 定量方式生物化学和动力学的详细变化 关于中枢神经系统轴突中轴突细胞骨架的研究，我们的 对影响再生能力的机制的理解 将会制造出神经元的。

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.