Exercise, neurotrophins and axon regeneration in the PNS

运动、神经营养因子和三七总皂甙中的轴突再生

基本信息

批准号：
7544515
负责人：
Arthur W. English
金额：
$ 30.12万
依托单位：
EMORY UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-01-19 至 2011-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7544515
关键词：
Address Afferent Neurons Allografting Animal Model Attention Axon Biological Models Brain Brain-Derived Neurotrophic Factor Clinical Confocal Microscopy Dependence Development Effectiveness Electric Stimulation Exercise Goals Growth Health Hour Injury Intervention Knockout Mice Label Lesion Mediating Methods Modality Motor Motor Endplate Motor Neurons Mus Muscle Natural regeneration Nerve Nervous System Trauma Neuraxis Neurons Neurotrophic Tyrosine Kinase Receptor Type 2 Operative Surgical Procedures Outcome Peripheral Peripheral Nerves Peripheral Nervous System Peripheral nerve injury Production Proteins Recovery of Function Research Personnel Sensory Signal Transduction Skeletal Muscle Specificity Speed Spinal Spinal Cord Synapses Therapeutic Time Time Study Training Transgenic Mice Transgenic Organisms Treatment Protocols Walking axon growth axon regeneration base cost design disability functional outcomes improved injured neural circuit neuromuscular neurotrophic factor novel programs receptor reinnervation repaired research study sedentary synaptogenesis

项目摘要

The two reasons most often given for the generally poor functional outcomes observed after peripheral nervous system (PNS) injury are that regenerating axons in peripheral nerves grow slowly and that muscles are often reinnervated by functionally inappropriate motoneurons. Electrical stimulation (ES) of the cut nerve at the time of its surgical repair promotes a significant enhancement of the growth of regenerating axons that is mediated by neuronal neurotrophins. However, there are many circumstances in which ES could be used and ES also results in an increase in muscle reinnervation by functionally inappropriate motoneurons. Exercise promotes BDNF expression in the brain and spinal cord and this could result in a stimulation of the growth of regenerating axons. The goal of this project is to compare the effects of one form of exercise, treadmill training, to those of ES on axon regeneration in peripheral nerves. A combination of transgenic and knockout mice will be used as a novel model system to investigate whether an exercise- induced enhancement of the growth of regenerating axons is mediated by neuronal neurotrophins. By comparing the effects of treadmill training on axon regeneration directly to those produced by ES, we will evaluate whether the enhancement of axon regeneration produced is similar. Synapse re-formation is a critical part of functional recovery after injury to the PNS, and without intervention, it takes longer than it takes regenerating axons to grow sufficiently to reach the muscles. We will compare the effect of ES and treadmill training on the time course of neuromuscular synapse re-formation in transgenic mice. Because it activates motoneurons naturally via their intrinsic neural circuits, exercise could be a way of enhancing regeneration with less functionally inappropriate reinnervation of muscles than noted with ES. The specificity of reinnervation of four different muscle targets will be compared, using retrograde fluorescent labeling methods, in untreated, electrically stimulated, and treadmill trained mice. Exercise has the potential to ameliorate both of the major issues contributing to poor functional recovery from lesions to the PNS. Its potential for clinical use with low cost and very high benefit is great. This project provides a unique opportunity to provide answers important to questions that will strengthen the basis for such clinical use.

外围后观察到的最常见的功能结果通常给出的两个原因神经系统（PNS）损伤是外周神经中再生轴突生长缓慢，肌肉通常通过功能不合适的运动神经元加剧。切割的电刺激（ES）神经在手术修复时，可促进再生的显着增强由神经元神经营养蛋白介导的轴突。但是，在许多情况下可以使用，ES还通过功能不合适而导致肌肉加剧增加运动神经元。运动促进BDNF在大脑和脊髓中的表达，这可能导致刺激再生轴突的生长。该项目的目的是比较一个项目的影响锻炼形式，跑步机训练，对周围神经中轴突再生的锻炼形式。组合转基因和基因敲除小鼠将被用作一种新型模型系统，以研究运动是否存在诱导的再生轴突生长增强是由神经元神经营养蛋白介导的。经过将直接的跑步机训练对轴突再生的影响与ES产生的轴突再生的影响，我们将评估产生的轴突再生的增强是否相似。突触重建是一个受伤后功能恢复的关键部分，如果没有干预，则需要的时间比服用再生轴突足够生长以达到肌肉。我们将比较ES和在转基因小鼠中神经肌肉突触重建的时间过程中的跑步机训练。因为它通过其内在的神经回路自然激活运动神经元，运动可能是增强的一种方式与ES相比，再生的功能不合适的肌肉不适当地增强肌肉。这使用逆行荧光，将比较四个不同肌肉靶标的重新支配的特异性在未处理，电刺激和跑步机训练的小鼠中使用标记方法。运动有潜力改善两个主要问题，导致功能不佳从病变到PNS的功能恢复不良。它是低成本和高收益的临床使用潜力是很大的。该项目提供了独特的有机会为问题提供重要的答案，这些问题将加强这种临床使用的基础。