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

• 批准号: 7848612
• 负责人: Arthur W. English
• 金额: $ 1.76万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-01-19 至 2010-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7848612
• 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

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.

外周血管移植术后观察到的功能结局普遍较差的两个最常见原因是 神经系统（PNS）损伤是周围神经再生轴突生长缓慢， 经常被功能不正常的运动神经元重新支配。切口电刺激（ES） 神经在其手术修复时促进再生的生长的显著增强， 轴突，由神经元神经营养因子介导。然而，在许多情况下， ES也会导致功能不适当的肌肉神经再支配增加， 运动神经元运动促进脑源性神经营养因子在大脑和脊髓中的表达，这可能导致 刺激再生轴突的生长。这个项目的目标是比较一个 运动形式、跑台训练、ES对周围神经轴突再生的影响。的组合 的转基因和基因敲除小鼠将被用作一种新的模型系统，以调查是否运动- 再生轴突生长的诱导增强由神经元神经营养素介导。通过 比较踏车训练对轴突再生的直接影响和ES产生的影响，我们将 评估所产生的轴突再生的增强是否相似。突触重建是一种 PNS损伤后功能恢复的关键部分，如果不进行干预， 需要再生轴突才能长到足够长的肌肉。我们将比较ES和 跑台训练对转基因小鼠神经肌肉突触重建的时间进程的影响。因为它 通过内在的神经回路自然地激活运动神经元，运动可能是一种增强运动神经元的方法。 与ES相比，肌肉的再生具有较少的功能不适当的神经再支配。的 将使用逆行荧光技术比较四种不同肌肉靶点的神经再支配特异性。 标记方法，在未经处理的，电刺激，和跑步机训练的小鼠。运动有潜力 以改善导致从病变到PNS的功能恢复不良的两个主要问题。其 成本低、效益很高的临床应用潜力巨大。该项目提供了一个独特的 有机会提供重要问题的答案，这将加强此类临床使用的基础。