DEVELOPMENT AND PATHOLOGY OF AXONS AND MYELIN

该提案要求支持一项持续的计划，该计划将审查 正常和病理性神经轴索膜的发育 纤维，以及轴突膜分化与胶质细胞的关系 联合和髓鞘形成。在过去的两年里，我们的研究引领了 在以下方面取得进展：i)中枢神经系统发育的生理学 有髓纤维；II)发育中央轴突的膜超微结构 有髓纤维；III)神经胶质细胞中轴突和轴膜的发育 缺乏环境；iv)髓鞘形成过程中的轴突-神经胶质关系；v) 再生轴突生理学；vi)脱髓鞘纤维生理学； Vii)运动轴突和感觉轴突的生理分化；viii) 非均匀纤维的导电特性。的主要成果之一 这些研究是对中国经济结构重组的证明 轴突膜发育过程中的有髓纤维。到目前为止， 这种轴突膜分化与轴突胶质细胞的关系 协会的研究还不够深入。我们现在计划研究一下 轴突膜的分化及其依赖关系 视神经和脊髓发育过程中神经胶质联系的分化 电源线。这些研究将利用几种互补的技术 (冷冻骨折、细胞化学、电生理学、H3毒素结合) 观察正常轴突和纤维中轴突膜的发育。 它们是在神经胶质细胞缺乏的环境中发展起来的。我们计划，在 这些研究，以考察分化中的事件顺序 有髓纤维的轴突膜，并确定是否(和是否 因此，具有什么时间进程和特点)节点和节点间 随着神经胶质细胞的延迟包膜，可以形成细胞膜。 我们还计划调查H3STX的发展与 轴膜的结合和冷冻断裂的超微结构。这些研究 将提供有关有髓轴突正常发育的信息， 以及被剥夺了神经胶质接触的轴突的特征。我们 相信这些结果将与理解 膜的可塑性可能在脱髓鞘疾病中起重要作用。

This proposal requests support for a continuing program which will examine the development of the axon membrane in normal and pathological nerve fibers, and the relationship of axon membrane differentiation to glial association and myelination. Over the past two years, our studies have led to progress in the following areas: i) physiology of developing CNS myelinated fibers; ii) axon membrane ultrastructure of developing central myelinated fibers; iii) axonal and axolemmal development in a glial deficient environment; iv) axo-glial relationships during myelination ; v) physiology of regenerating axons; vi) physiology of demyelinated fibers; vii) physiological differentiation of motor and sensory axons; viii) conduction properties of inhomogeneous fibers. One of the major results of these studies is the demonstration of a structural reorganization of the axon membrane during the development of myelinated fibers. To date, the relationship between this axon membrane differentiation and axo-glial association has remained incompletely studied. We now plan to examine the differentiation of the axon membrane, and the dependence of this differentiation on glial association, in developing optic nerve and spinal cord. These studies will utilize several complementary techniques (freeze-fracture, cytochemistry, electrophysiology, H3 saxitoxin binding) to examine axon membrane development both in normal axons, and in fibers which have developed in a glial cell deficient environment. We plan, in these studies, to examine the sequence of events in the differentiation of the axonal membrane of myelinated fibers, and to determine whether (and if so, with what time course and characteristics) nodal and internodal membrane can develop in response to delayed ensheathment with glial cells. We also plan to investigate the relationship between development of H3 STX binding, and freeze-fracture ultrastructure of the axolemma. These studies will provide information about the normal development of myelinated axons, and the characteristics of axons which are deprived of glial contact. We believe that these results will be relevant to understanding mechanisms of membrane plasticity which may be important in the demyelinating diseases.