FORMATION AND ELIMINATION OF NERVE-MUSCLE SYNAPSES

神经肌肉突触的形成和消除

• 批准号: 3395468
• 负责人: JEFFREY L DENBURG
• 金额: $ 16.69万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 财政年份: 1978
• 资助国家: 美国
• 起止时间: 1978-04-01 至 1991-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3395468
• 关键词: axon; axon reaction; cell cell interaction; cockroach; electrophysiology; glycoproteins; histochemistry /cytochemistry; hybridomas; immunochemistry; immunofluorescence technique; innervation; interneurons; membrane activity; monoclonal antibody; motor neurons; muscle; nervous system regeneration; neural transmission; neuroanatomy; neurochemistry; neurogenesis; neuromuscular junction; neuromuscular system; nonmammalian vertebrate embryology; synapses; tissue /cell culture

The formation of patterned connections between motor neurons and muscles during development in the vertebrates requires specific cell-cell recognition as well as an editing mechanism of synaptic elimination. The complex anatomy of even this relatively simple system is such that an understanding of these phenomena at the cellular and molecular levels is difficult. The leg neuromuscular system of the cockroach is even simpler with muscles innervated by one or a small number of motor neurons. When the axons of these motor neurons are cut, they regenerate and eventually reform synapses with just the original target muscles. However, at early stages of regeneration inappropriate synapses form. The apparent specificity arises from the selective elimination of these mistakes. The cockroach serves as a model system in which to examine common developmental processes at the cellular and molecular levels. The ability to distinguish among target muscles indicates that there are molecular differences between individual motor neurons and between individual muscles. Monoclonal antibodies are available that bind to the surfaces of axon terminals of identified motor neurons. These will be used to purify the antigens and to demonstrate a function for them during regeneration. Tissue culture and immunohistochemical techniques will be used to test the hypothesis that the specificity of the interaction between motor neurons and muscles arises from a selective enhancement of growth and sprouting of axons only in their appropriate target muscles. Recombinant DNA techniques will be used to characterize the candidate recognition macromolecules. The information acquired on the mechanism of the successful regeneration of cockroach motor neurons will also be applicable to attempts to increase the probability of obtaining such regeneration in humans. Such knowledge would be helpful for the treatment of paraplegia, neuromuscular disorders, multiple sclerosis and other neurological disorders involving injury such as strokes and head injury.

运动神经元和 脊椎动物发育过程中的肌肉需要特定 细胞电池识别以及突触的编辑机制 消除。 这个相对简单的复杂解剖结构 系统使得对这些现象的理解 细胞和分子水平很难。 腿神经肌肉 蟑螂的系统甚至更简单，肌肉支配 一个或少量的运动神经元。 当这些轴突 运动神经元被切割，它们再生并最终改革 仅与原始目标肌肉突触。 但是，早点 再生阶段不适当的突触形式。 明显 特异性来自选择性消除这些 错误。 蟑螂用作模型系统 检查细胞和 分子水平。 区分目标肌肉的能力表明 单个运动神经元之间存在分子差异 以及在个体肌肉之间。 单克隆抗体是 可用与已鉴定的轴突端子的表面结合的可用 运动神经元。 这些将用于净化抗原和 在再生过程中为它们展示功能。 组织 培养和免疫组织化学技术将用于测试 假设电机之间相互作用的特异性 神经元和肌肉来自选择性增长 仅在适当的目标肌肉中发芽轴突。 重组DNA技术将用于表征 候选识别大分子。 获取有关成功机制的信息 蟑螂运动神经元的再生也适用于 试图增加获得这种再生的可能性 在人类中。 这样的知识将有助于治疗 截瘫，神经肌肉疾病，多发性硬化症和其他 涉及损伤的神经系统疾病，例如中风和头部 受伤。