MECHANISM OF NEURITE FORMATION

神经突形成机制

• 批准号: 3411785
• 负责人: Cara-Lynne Schengrund
• 金额: $ 13.75万
• 依托单位: PENNSYLVANIA STATE UNIV HERSHEY MED CTR
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-08-01 至 1993-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3411785
• 关键词: autoradiography; brain; brain mapping; carbohydrate receptor; cell differentiation; gangliosides; laboratory rat; membrane activity; nervous system regeneration; neuroblastoma; neurogenesis; neurons; oligosaccharides; phosphorylation; tissue /cell culture

Gangliosides have been found to enhance neuritogenesis by neuroblastoma cel s in vitro , and to enhance nerve regeneration in vivo. Recently the oligosaccharide moieties of gangliosides have also been found to enhance neuritogenesis by neuroblastoma cells, suggesting the presence of a cell surface receptor. This hypothesis is supported by the observation that viab e neural retina cells can bind to gangliosides adsorbed to plastic via a trypsin sensitive mechanism. This proposal asks two fundamental questions concerning these observations: 1) how much exogenous ganglioside actually reaches the lesioned area within the brain where it putatively enhances neuritogenesis?; and 2) how does the ganglioside interact with the neuroblastoma or neuron? To answer the first question autoradiographic experiments will be carried out to determine the distribution of labeled ganglioside in the brains of lesioned and unlesioned rats. To answer the second question, experiments will be carried out to determine whether ganglioside responsive neuroblastoma cells have cell surface receptors capable of recognizing the oligosaccharide moiety of the appropriate gangli - side. If receptors are identified they will be isolated and characterized. Primary cultures of neurons will also be assayed for the presence of ganglioside-oligosaccharide cell surface receptors. To determine the effect of this interaction on "differentiation" properties defined as associated with neuronal maturation will be monitored. To determine a possible mechani m for transmitting the binding into an intracellular response, the effect of the ganglioside and the corresponding oligosaccharide on the phosphorylatio activity of the cell plasma membranes will be determined.

已经发现神经节苷脂可以增强神经母细胞瘤细胞的轴突发生， S 在体外和体内增强神经再生。最近 还发现神经节苷脂的寡糖部分可增强 神经母细胞瘤细胞的神经突生成，表明存在细胞 表面受体这一假设得到了以下观察结果的支持： e 神经视网膜细胞可以通过一种结合剂与吸附在塑料上的神经节苷脂结合， 胰蛋白酶敏感机制这一提议提出了两个基本问题 关于这些观察：1）实际上有多少外源性神经节苷脂 到达大脑中的病变区域， 神经突发生？以及2）神经节苷脂如何与 神经母细胞瘤还是神经元回答第一个问题放射自显影 将进行实验，以确定标记的分布 神经节苷脂在损伤和未损伤大鼠脑中的表达。回答 第二个问题，将进行实验，以确定是否 神经节苷脂反应性神经母细胞瘤细胞具有细胞表面受体 能够识别适当神经节的寡糖部分， - 的方面想如果识别出受体，将对其进行分离和表征。 还将测定神经元的原代培养物中是否存在 神经节苷脂寡糖细胞表面受体。以确定影响 这种相互作用的“分化”属性定义为相关的 将监测神经元成熟。确定可能的机制 M 为了将结合传递到细胞内反应中， 神经节苷脂和相应的寡糖对磷酸化 将测定细胞质膜的活性。