OLIGODENDROCYTE ONTOGENY AND DIFFERENTIATION

少突胶质细胞个体发育和分化

• 批准号: 3400079
• 负责人: ELISA M BARBARESE
• 金额: $ 15.95万
• 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 1993-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3400079
• 关键词: axon; cell differentiation; dendrites; enzyme linked immunosorbent assay; gene expression; gene mutation; genetic manipulation; genetic translation; immunochemistry; immunofluorescence technique; laboratory mouse; messenger RNA; monoclonal antibody; myelin; myelin basic proteins; myelination; neuroanatomy; neurogenesis; 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 dendritic processes each terminating in a myelin sheath. Myelin components are regionally distributed within the oligodendrocyte by translocation, and assembled at the site of myelin formation. The synthesis of myelin thus requires sorting mechanisms by which specific myelin components are recognized by the oligodendrocyte cellular machinery and delivered to the site of myelin assembly. This process may be regulated by neuronal signals upon interaction of an oligodendrocyte dendrite with an axon. We propose to use cell culture, genetic mutations, biochemical, immunochemical, biophysical and molecular biology techniques to study the mechanisms regulating the assembly of myelin basic protein, a major structural component of myelin, into the oligodendrocyte myelin membrane during oligodendrocyte differentiation in primary culture with neurons. Our long term objectives are to delineate the various steps in myelin morphogenesis, to determine their pattern of regulation and identify the molecular mechanisms underlying them. 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 viral infections.

髓鞘是围绕着轴突的多层膜鞘。 中枢神经系统和三叉神经核通过以下途径促进神经冲动的快速传导 跳跃传导。在中枢神经系统，少突胶质细胞合成， 组装和维护髓鞘作为一个复杂的解剖和 功能结构。每个少突胶质细胞延伸出几个树突状 每个突起都以髓鞘为终末。髓鞘成分是 通过易位在少突胶质细胞内区域分布，以及 聚集在髓鞘形成的地方。因此髓磷脂的合成 需要特定的髓鞘组分的分类机制 由少突胶质细胞的细胞器识别并交付给 髓鞘组装的位置。这一过程可能由神经元调节。 少突胶质细胞树突与轴突相互作用时的信号。我们 建议使用细胞培养、基因突变、生化、 免疫化学、生物物理和分子生物学技术研究 调节髓鞘碱性蛋白组装的机制是一种主要的 髓鞘结构成分，进入少突胶质细胞髓磷脂细胞膜 在有神经元的原代培养中进行少突胶质细胞分化。 我们的长期目标是描绘髓鞘的各个步骤 形态发生，以确定它们的调节模式并识别 它们背后的分子机制。更好地理解 髓鞘形成的过程，最终髓鞘的维持和 修复，可能导致治疗、免疫化学、药物或 遗传性，适用于患有中枢神经系统脱髓鞘疾病的患者 和PNS，如多发性硬化症和格林-巴利综合征，以及 放射治疗后出现脱髓鞘症状的患者 和病毒感染。