CELLULAR CORRELATES OF AXONAL SPROUTING

哺乳动物下丘脑大细胞神经分泌神经元 系统（MNS）表现出异常强劲再生能力。 它 多年前就知道它们可以再生被切断的轴突 垂体柄切片，这个实验室最近证明 未受伤的MNS神经元的轴突终末也将经历强烈的 成年大鼠的补偿性发芽。 在摧毁一个 下丘脑-神经垂体束的一半通过单侧 下丘脑病变，完整的对侧MNS神经元的轴突生长 使神经叶（NL）的轴突群恢复到接近 90天内达到正常水平。 本项目的长期目标 是确定MNS的哪些特殊特性提供了 这种可塑性。 NL是一个大大简化的肽能末端 场，主要由神经分泌轴突，垂体细胞（一种形式的 星形胶质细胞）和小胶质细胞。 因此这个系统的组织 特别是有助于研究补偿性的两个方面， 发芽：神经元活动的作用，以及胶质细胞的影响 细胞 实现该项目的具体目标将提供一个 详细比较伴随轴突的细胞事件 退化和发芽在这个新的模型与那些已知发生在 对脑损伤的反应。 这是用形态测量学 和免疫细胞化学技术：（1）定量胶质细胞的程度 （2）在芽生反应过程中，NL的增生和肥大; 确定巨噬细胞特异性抗原的表达模式， 神经胶质细胞;（3）确定神经胶质细胞的表达是否改变， 胶质酸性蛋白、波形蛋白和胶质透明质酸结合 蛋白的表达，并研究生长激素的表达。 相关蛋白GAP-43在这些神经元发芽过程中。 结果 这些研究将为今后的努力建立必要的数据基础 通过施用以下物质来改变发芽反应的过程： 肽激素和细胞表面受体抗体，粘附 由于几乎所有的神经疾病都涉及某种程度的 组织退化，增加细胞生物学知识， 对中枢神经系统损伤的潜在代偿性反应对于 有效治疗的最终设计。

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.