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。 它有 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神经元的轴突末梢也将经历强烈的 成年大鼠的补偿性发芽。 在摧毁了一半之后， 下丘脑-神经垂体束通过单侧下丘脑 损伤后，完整的对侧MNS神经元的轴突长出新芽， 神经叶（NL）的轴突数量在90 天 该项目的长期目标是确定什么特别的 MNS的特性为这种可塑性提供了基础。 民族解放军 是一个大大简化的肽能末端区域，主要由以下组成： 神经分泌轴突、垂体细胞（星形胶质细胞的一种形式）和小胶质细胞。 因此，该系统的组织特别适合于 补偿发芽的两个方面的调查： 神经元活动和神经胶质细胞的影响。 履行 本提案的具体目标将提供以下方面的详细比较： 伴随轴突变性和发芽的细胞事件， 这种新的模型与那些已知的脑损伤反应发生。 这 将使用形态测量和免疫细胞化学技术完成 目的：（1）量化NL中神经胶质增生和肥大的程度 在发芽反应期间;（2）确定表达模式， 巨噬细胞特异性抗原的神经胶质细胞;（3）确定是否 胶质细胞酸性蛋白、波形蛋白和胶质细胞 垂体细胞的透明质酸结合蛋白伴随出芽;和（4）， 比较催产素和加压素引起的轴突发芽程度 神经元，并研究生长相关蛋白GAP-43的表达 被这些神经元吸收。 这些研究的结果将建立 为今后努力改变这一进程提供必要的数据基础。 通过施用肽激素和抗体的发芽反应 细胞表面受体、粘附分子等。 神经障碍涉及一定程度的组织变性，增加 对损伤的代偿反应的细胞生物学知识 对最终设计有效的治疗方法至关重要。

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 lesion, 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 proposal will provide a detailed comparison between the cellular events which accompany axonal degeneration and sprouting in this new model with those known to occur in response to brain injury. This will be 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 pituicytes accompanies sprouting; and (4), compare the extent of axonal sprouting by oxytocin versus 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.