OLIGODENDROCYTE ONTOGENY AND DIFFERENTIATION

少突胶质细胞个体发育和分化

基本信息

批准号：
3400078
负责人：
ELISA M BARBARESE
金额：
$ 15.43万
依托单位：
UNIVERSITY OF CONNECTICUT SCH OF MED/DNT
依托单位国家：
美国
项目类别：
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/3400078
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

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

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项目摘要

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，组装并保持髓鞘作为复杂的解剖学和功能结构。每个少突胶质细胞延伸几个树突状处理每个终止在髓鞘中的终止。髓鞘成分是通过易位在少突胶质细胞中分布的区域分布，在髓鞘形成的位置组装。因此，髓磷脂的合成需要对特定髓磷脂成分的分类机制被少突胶质细胞蜂窝机械识别并传递到髓鞘组件的位置。此过程可能受神经元调节少突胶质细胞与轴突相互作用后的信号。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磷脂碱性蛋白组装的机制，这是一个主要的髓磷脂的结构成分，进入少突胶质细胞髓磷脂膜在神经元原发性培养中的少突胶质细胞分化过程中。我们的长期目标是描述髓磷脂的各个步骤形态发生，确定其调节模式并确定它们的分子机制。更好地理解髓鞘形成的过程，最终维修，可能导致疗法，免疫化学，药物或遗传，患有中枢神经系统脱髓鞘疾病的患者以及多发性硬化症和吉兰 - 巴里综合症等PN，以及治疗辐射后有脱髓鞘状况的患者和病毒感染。