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。它有 多年来一直知道它们可以再生被切断的轴突 脑垂体柄切片，这个实验室最近证明了 未受损的MNS神经元的轴突终末也将经历强健的 成年大鼠的代偿性发芽。在毁掉一半之后 经单侧下丘脑的下丘脑-神经垂体束 损伤后，完整的对侧MNS神经元的轴突长出萌芽，然后再返回 神经叶(NL)轴突数量在90内降至接近正常水平 几天。这个项目的长期目标是确定什么特殊的 MN的特性为这种塑性提供了基础。民族解放阵线 是一种极大简化的肽能终末区域，主要由 神经分泌轴突、垂体细胞(星形胶质细胞的一种)和小胶质细胞。 因此，这一系统的组织结构特别适合于 关于补偿萌发的两个方面的考察： 神经元活性，以及神经胶质细胞的影响。履行 这项提案的具体目标将提供以下详细比较 伴随着轴突变性和发芽的细胞事件 这种新的模式与那些已知发生的脑损伤反应有关。这 将使用形态测量和免疫细胞化学技术来完成 目的：(1)定量测定下丘脑核胶质细胞增生和肥大的程度。 在萌发反应过程中；(2)确定 巨噬细胞特异性抗原的表达；(3)确定 胶质纤维酸性蛋白、波形蛋白和胶质细胞表达的改变 脑下垂体细胞的透明质酸结合蛋白伴随发芽；以及(4)， 催产素和加压素对轴突萌发程度的比较 并研究生长相关蛋白GAP-43的表达 在这些神经元的萌芽过程中。这些研究的结果将确定 必要的数据库，为未来的努力改变 给予多肽激素和抗体的萌发反应 细胞表面受体、黏附分子等。因为几乎所有 神经疾病涉及到一定程度的组织退变，增加 损伤代偿性反应的细胞生物学知识 对中枢神经系统的研究对于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.