THE ROLE OF ZINC IN NEURONAL DEVELOPMENT

细胞骨架的主要成分；微管、神经丝和 微丝在细胞的结构和功能完整性中起着关键作用。 神经细胞突起(轴突和树突)。组件和/或缺陷 这些因素的相互作用可能有助于 退行性神经元病。虽然大量的信息已经被 积累了促进集结和稳定的因素 无细胞系统中的细胞骨架成分，它们之间的关系 分化神经元中对细胞骨架的影响因素仍然难以捉摸。 最近，我们报道了锌在竖井中特别丰富 在细胞骨架密集的区域发育神经突起 在转化和原代神经元培养中的框架。这个 锌与发育中的神经突起的联系是特别的 兴趣，因为已经证明：1)锌与 微管在各种生物系统中，2)锌促进 无细胞体系中微管的组装和稳定，3)a 胚胎发育过程中锌的缺乏会导致脑部疾病 发育异常和4)锌中毒导致脑发育异常 微管结构，并导致神经细丝的积聚。 受影响动物的大脑。这些结果表明，锌在人体内起着 神经细胞相互作用在神经细胞突起发育中的作用 有微管。该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) 研究锌与其他元素(钙、镁、磷、钙、镁、磷)的分布。 S，氯，钾和钠)在神经突起中的作用，2)研究锌在 神经突起的形成和稳定；3)检查 锌的吸收、分布和转运的时间变化 神经元发育。为实现这些目标，我们将采用：a) 培养转化神经元和原代神经元作为神经模型系统，b) 延时电影显微照相术记录神经生长的变化 工艺，c)全细胞透射电子显微镜和 电子探针微分析串联检测细胞骨架 并对锌和其他元素的水平进行量化， 和d)放射性标记锌以检查摄取和转运 锌在发育的神经突起中的作用。

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.