OLIGODENDROCYTE ONTOGENY AND DIFFERENTIATION

少突胶质细胞个体发育和分化

• 批准号: 6126098
• 负责人: ELISA M BARBARESE
• 金额: $ 21.46万
• 依托单位: UNIVERSITY OF CONNECTICUT SCH OF MED/DNT
• 依托单位国家: 美国
• 财政年份: 1984
• 资助国家: 美国
• 起止时间: 1984-12-01 至 2000-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6126098
• 关键词: cell differentiation; cytoskeleton; developmental neurobiology; gene mutation; immunocytochemistry; intracellular transport; laboratory mouse; messenger RNA; myelin; myelin basic proteins; myelination; neuronal transport; oligodendroglia; protein biosynthesis; protein transport; tissue /cell culture

Myelin is the multilamellar membranous sheath that surrounds axons in the CNS and the PNS, contributing to fast conduction of nerve impulses by saltatory conduction. In the CNS, the oligodendrocyte synthesizes, assembles, and maintains the myelin sheath as a complex anatomical and functional structure. Each oligodendrocyte extends several processes each terminating in a myelin sheath. In order to achieve the production and directional assembly of this large amount of membrane, the cell spatially organizes its synthetic machinery through the redistribution of its cytoskeletal elements. This hypothesis will be tested by microscopic analysis of the distribution of cellular organelles and cytoskeletal elements in oligodendrocytes at various stages of myelin formation. Myelin components are regionally distributed within the oligodendrocytes and the myelin sheath. Thus, the synthesis of myelin requires sorting mechanisms by which specific myelin components are recognized by the oligodendrocyte cellular machinery and delivered to the site of myelin assembly. The sorting of myelin basic protein takes place at the level of its mRNA, which is transported down the processes to the myelin sheath in a complex associated with the oligodendrocyte cytoskeleton. We propose to characterize this complex by the use of in situ hybridization, immunocytochemistry, E.N. localization, and metabolic inhibitors. Our long term objectives are to delineate and characterize the various steps in myelin morphogenesis. A better understanding of the process of myelin formation, and eventually of myelin maintenance and repair, could lead to therapies, immunochemical, pharmaceutical, or genetic, for patients afflicted with demyelinating diseases of the CNS and PNS, such as multiple sclerosis and Guillain-Barre syndrome, and for patients with demyelinating conditions following therapeutic irradiation and chemotherapy or viral infections.

髓鞘是周围轴突的多层膜膜 中枢神经系统和PNS，有助于快速传导神经冲动 盐传导。 在中枢神经系统中，少突胶质细胞合成， 组装，并保持髓鞘为复杂的解剖学和 功能结构。 每个少突胶质细胞延长了几个过程 终止在髓鞘中。 为了实现生产和 该大量膜的定向组装在空间上 通过重新分布来组织其合成机械 细胞骨架元素。 该假设将通过显微镜进行检验 细胞细胞器和细胞骨架的分布分析 在髓鞘形成的各个阶段的少突胶质细胞中的元素。 髓磷脂成分在少突胶质细胞内分布 还有髓鞘。 因此，髓磷脂的合成需要分类 特定的髓磷脂成分被识别的机制 少突胶质细胞蜂窝机械并运送到髓磷脂部位 集会。 髓磷脂碱性蛋白的分类发生在 它的mRNA，将过程从过程中运送到髓鞘中 与少突胶质细胞细胞骨架有关的复合物。我们建议 通过使用原位杂交来表征这种复合物， E.N.免疫细胞化学定位和代谢抑制剂。 我们的长期目标是描绘和表征各种目标 髓磷脂形态发生的步骤。 更好地理解 髓鞘形成，最终是髓鞘维护和维修，可以 导致治疗，免疫化学，药物或遗传学 患有中枢神经系统和PN的脱髓鞘疾病的患者，例如 多发性硬化症和Guillain-Barre综合征，适用于患者 治疗辐射和 化学疗法或病毒感染。