NERVE GROWTH FACTOR--AXONAL AND SYNAPTIC CHANGES IN THE SPINAL CORD

神经生长因子——脊髓的轴突和突触变化

• 批准号: 3922804
• 负责人: CLAIRE E. HULSEBOSCH
• 金额: --
• 依托单位: UNIVERSITY OF TEXAS MED BR GALVESTON
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3922804
• 关键词: antibody; axon; calcitonin gene related peptide; denervation; dorsal column; histochemistry /cytochemistry; immunochemistry; immunoglobulins; laboratory rat; nervous system regeneration; neuroanatomy; neurogenesis; neuronal guidance; neurotrophic factors; spinal cord; substance P; synapses

This proposal is designed to extend studies of axonal sprouting induced by antibodies to Nerve Growth Factor (ANTI-NGF). Data collected in this laboratory demonstrate that the central processes of sensory neurons sprout after surgical denervation. Daily administration of Nerve Growth Factor (NGF) did not enhance the sprouting. Conversely, daily administration of ANTI- NGF increased the sensory axon sprouting by 50% in surgically denervated and uninjured mammals. The objectives of the current projects are to extend this work by examining the spinal white matter and the dorsal horn, one of the synaptic sites of the sensory neurons. During the first year of the grant, the axonal number in Lissauer's tract were determined. Specific aims of the proposed project are 1) to quantify the effects on axonal numbers in the dorsal columns and determine the proportion of sensory and propriospinal fibers and 2) to quantify the effects on synaptic number in the dorsal horn of uninjured mammals given ANTI-NGF. The methods will be ultrastructural quantitation of the myelinated and unmyelinated axons of the spinal white matter and stereological techniques applied at the ultrastructural level for the quantitation of synapses in the dorsal horn. Given the intraspinal sprouting may be related to functional recovery and that manipulating levels of endogenous NGF may enhance intraspinal sprouting, these studies may lead to manipulations that are clinically applicable.

该提案旨在扩展轴突萌芽的研究 由神经生长因子（ANTI-NGF）抗体诱导。 数据 该实验室收集的数据表明，中央 手术去神经后感觉神经元的突起萌芽。 每天服用神经生长因子（NGF）不会 增强发芽。 相反，每天服用抗 NGF 通过手术使感觉轴突萌发增加了 50% 去神经且未受伤的哺乳动物。 当前的目标 项目将通过检查脊柱白来扩展这项工作 物质和背角，突触部位之一 感觉神经元。 在拨款的第一年，轴突 确定了利绍尔区域中的数量。 具体目标 拟议的项目是 1) 量化对轴突数量的影响 在背柱并确定感觉和 本体脊髓纤维和 2) 量化对突触的影响 给予 ANTI-NGF 的未受伤哺乳动物的背角中的数量。 该方法将是超微结构定量 脊髓白质的有髓和无髓轴突以及 体视学技术应用于超微结构水平 背角突触的定量。 鉴于椎管内出芽可能与功能有关 恢复和控制内源性 NGF 的水平可能 增强椎管内出芽，这些研究可能会导致 临床上适用的操作。