THE ROLE OF ZINC IN NEURONAL DEVELOPMENT

细胞骨架的主要组成部分;微管，神经丝和 微丝在结构和功能完整性中发挥关键作用 神经细胞过程（轴突和树突）。 装配缺陷和/或 这些因素的相互作用可能有助于病因 神经退行性疾病 虽然大量的信息已经 积累的因素，促进组装和稳定的 在无细胞系统中的细胞骨架成分，这些 在分化的神经元中细胞骨架的因子仍然是难以捉摸的。 最近，我们报道说，锌是特别丰富的轴， 在含有致密细胞骨架的区域中发育神经突起 在转化和原代神经元培养物中的框架。 的 锌与发育中的神经过程的联系是特别的， 感兴趣，因为已经表明：1）锌与 在各种生物系统中的微管，2）锌促进 无细胞系统中微管的组装和稳定，3）a 在胚胎发育过程中缺乏锌会导致大脑 发育异常和4）锌中毒导致异常的 微管结构，并导致神经丝的积累， 受影响动物的大脑 这些结果表明，锌发挥作用， 通过其相互作用在神经细胞过程发育中的作用 与微管。 本项目的总体目标是确定 锌在神经元发育中的作用 具体目标是：1） 为了检查锌沿着其它元素（Ca，Mg，P， S、Cl、K和Na）在神经过程中的作用; 2）研究锌在神经过程中的作用。 形成和稳定的神经过程和3）检查 锌的吸收、分布和转运的时间变化 神经元发育 为了实现这些目标，我们将采用： 作为神经模型系统的转化和原代神经元的培养物，B） 延时电影显微摄影术记录神经生长的变化 过程，c）全细胞透射电子显微镜，以及 电子探针微分析串联检查细胞骨架 成分并定量锌和其他元素的水平， 和d）放射性标记的锌，以检查摄取和转运 锌在发育中的神经过程。

Major components of the cytoskeleton; microtubules, neurofilaments and microfilaments play key roles in the structural and functional integrity of nerve cell processes (axons and dendrites). Defects in the assembly and/or interaction of these elements may contribute to the etiology of degenerative neuronal diseases. While substantial information has been accumulated on factors which promote the assembly and stabilization of cytoskeletal components in cell-free systems, the relationship of these factors to the cytoskeleton in differentiating neurons remains elusive. Recently, we reported that zinc is particularly abundant in the shaft of developing nerve processes in areas containing a dense cytoskeletal framework in both transformed and primary neuronal cultures. The association of zinc with developing nerve processes is of particular interest since it has been shown that: 1) zinc is associated with microtubules in a variety of biological systems, 2) zinc promotes the assembly and stabilization of microtubules in cell-free systems, 3) a deficiency of zinc during embryonic development results in brains with developmental anomalies and 4) zinc toxicity results in abnormalities of microtubule structure and leads to the accumulation of neurofilaments in the brains of affected animals. These results suggest that zinc plays a role in the development of nerve cell processes through its interaction with microtubules. The overall objective of this project is to determine the role of zinc in neuronal development. The specific objectives are: 1) to examine the distribution of zinc along with other elements (Ca, Mg, P, S, Cl, K and Na) in nerve processes, 2) to examine the role of zinc in the formation and stabilization of nerve processes and 3) to examine the temporal changes in the uptake, distribution and transport of zinc during neuronal development. To accomplish these objectives, we will employ: a) cultures of transformed and primary neurons as nerve model systems, b) time-lapse cinemicrography to document changes in growth of nerve processes, c) whole-cell transmission electron microscopy and electron-probe microanalysis in tandem to examine the cytoskeletal components and quantitate the levels of zinc and other elements, respectively, and d) radiolabelled zinc to examine the uptake and transport of zinc in developing nerve processes.