Gap Junctions and Connexins in Developing CNS

中枢神经系统发育中的间隙连接和连接蛋白

• 批准号: 6889074
• 负责人: JOHN E RASH
• 金额: $ 27.55万
• 依托单位: COLORADO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-05-01 至 2007-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6889074
• 关键词: cell cell interaction; confocal scanning microscopy; developmental neurobiology; freeze etching; gap junctions; glia; immunocytochemistry; intercellular connection; laboratory rat; locus coeruleus; membrane channels; membrane proteins; neurogenesis; neurons; newborn animals; polymerase chain reaction; protein structure; somesthetic sensory cortex; spinal cord

DESCRIPTION (provided by the applicant): Gap junctions are membrane specializations that link cells directly for electrical, ionic and metabolic communication. In the central nervous system of adult rats, gap junctions are abundant between glial (supporting) cells, but relatively few are present between neurons. During development, gap junctional coupling is strong between neurons and have been reported to occur between neurons and glial cells. An integrated approach using a combination of electron microscopic freeze-fracture immunocytochemistry, confocal microscopic immunocytochemistry, and single-cell RT-PCR will be used to identify the gap junction "connexin" protein molecules that are present in neurons and glia, determine if neurons share gap junctions with glia, and assay the distribution of neuronal gap junctions in early postnatal CNS. Gap junctions are thought to provide pathways for metabolic and regulatory molecules during the period of neuronal differentiation and maturation. Areas of the CNS to be examined are locus coeruleus, somatosensory cortex, and spinal cord. Obtaining accurate data regarding the composition and intercellular coupling relationships in those areas will be essential for understanding mechanisms regulating: (1) normal development of neurons and glia in the CNS; (2) postnatal organization and reorganization of neuronal circuits; (3) programmed cell death during normal sculpting of the neuron pools in early postnatal development; (4) neuronal synchronization and rhythmic bursting activity in developing and adult neurons; and (5) abnormal synchronous bursting activity, such as in epileptic seizures.

描述（由申请人提供）：间隙连接为膜连接 将细胞直接连接为电、离子和代谢的专门化 通信在成年大鼠的中枢神经系统中，缝隙连接是 在胶质（支持）细胞之间丰富，但相对较少 神经元之间。在发育过程中， 神经元，并已报道发生在神经元和神经胶质细胞之间。一个 结合电子显微冷冻断裂的综合方法 免疫细胞化学、共聚焦显微镜免疫细胞化学和单细胞 RT-PCR将用于鉴定差距连接“连接蛋白”蛋白分子 存在于神经元和神经胶质中，决定神经元是否共享缝隙连接， 与胶质细胞，并测定神经元间隙连接的分布在早期 出生后中枢神经系统。缝隙连接被认为是提供代谢途径， 神经元分化期间的调节分子， 成熟要检查的中枢神经系统区域是蓝斑、体感 皮质和脊髓。获得关于组成的准确数据， 这些区域的细胞间耦合关系对于 了解调控机制：（1）神经元和胶质细胞的正常发育 （2）出生后神经元回路的组织和重组; (3)在早期神经元池的正常雕刻过程中程序性细胞死亡 出生后发育;（4）神经元同步化和节律爆发 发育期和成年期神经元的活动;（5）异常同步爆发 活动，如癫痫发作。