CELLULAR CORRELATES OF AXONAL SPROUTING

哺乳动物下丘脑大细胞神经分泌神经元 系统(MN)表现出异常旺盛的再生能力。它 已经知道很多年了，它们可以再生被 脑垂体柄切片，这个实验室最近证明了 未受损伤的MNS神经元的轴突终末也将经历强大的 成年大鼠的代偿性发芽。在摧毁了一个 经单侧下丘脑-神经垂体束的一半 下丘脑损害，健侧MNS神经元轴突生长 将神经叶(NL)的轴突群返回到附近的萌芽 90天内达到正常水平。这个项目的长期目标是 就是确定跨国公司有哪些特殊特征提供了依据 对于这种可塑性。NL是一种大大简化的多肽能终末 视野，主要由神经分泌性轴突、垂体细胞(一种 星形胶质细胞)和小胶质细胞。因此，这一系统的组织 特别是对补偿的两个方面进行了考察 发芽：神经元活动的作用，以及神经胶质细胞的影响 细胞。该项目具体目标的实现将提供一个 伴随轴突的细胞事件的详细比较 在这种新的模式中退化和萌发，而那些已知发生在 对脑损伤的反应。这是使用形态测量学来完成的 和免疫细胞化学技术：(1)量化胶质细胞的程度 发芽反应过程中中枢神经的增殖和肥大； 通过测定巨噬细胞特异性抗原的表达模式 NL的神经胶质细胞；(3)确定神经胶质细胞的表达是否改变 纤维酸性蛋白、波形蛋白和胶质细胞透明质酸结合 通过加压素神经元的蛋白表达，并观察其生长情况 这些神经元在发芽过程中的相关蛋白GAP-43。结果： 这些研究将为今后的工作建立必要的数据库。 通过给药改变发芽反应的进程 抗细胞表面受体的多肽激素和抗体，黏附 分子等，因为几乎所有的神经障碍都涉及到某种程度的 组织退化，增加对细胞生物学的了解 中枢神经系统损伤的潜在代偿性反应对 有效疗法的终极设计。

The neurons of the mammalian hypothalamic magnocellular neurosecretory system (MNS) exhibit unusually vigorous regenerative capabilities. It has been known for many years that they can regenerate axons severed by pituitary stalk section, and this laboratory has recently demonstrated that the axon terminals of uninjured MNS neurons will also undergo robust compensatory sprouting in the adult rat. Following destruction of one half of the hypothalamo-neurohypophysial tract via a unilateral hypothalamic lesions, axons of intact contralateral MNS neurons grow sprouts which return the axon population of the neural lobe (NL) to near normal levels within 90 days. The long-term objective of this project is to determine what special characteristics of the MNS provide the basis for this plasticity. The NL is a greatly simplified peptidergic terminal field, composed primarily of neurosecretory axons, pituicytes (a form of astrocyte), and microglia. Thus the organization of this system especially lends itself to investigation of two aspects of compensatory sprouting: the role of neuronal activity, and the influence of glial cells. Fulfillment of the specific aims of this project will provide a detailed comparison between the cellular events which accompany axonal degeneration and sprouting in this new model with those know to occur in response to brain injury. This is being accomplished using morphometric and immunocytochemical techniques to: (1) quantify the extent of glial hyperplasia and hypertrophy in the NL during the sprouting response; (2) determine the pattern of expression of macrophage-specific antigens by glial cells of the NL; (3) determine if altered expression of glial fibrillary acidic protein, vimentin, and glial hyaluronate-binding protein by vasopressin neurons, and investigate the expression of Growth Associated Protein GAP-43 by these neurons during sprouting. Results of these studies will establish the necessary data base for future efforts to alter the course of the sprouting response by administration of peptide hormones and antibodies to cell surface receptors, adhesion molecules, etc. Since virtually all neural disorders involve some degree of tissue degeneration, increased knowledge of the cell biology underlying compensatory responses to injury of the CNS is crucial for the ultimate design of effective therapies.