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.

最常见的两个原因是外周手术后观察到的普遍较差的功能结果 神经系统(PNS)损伤是指周围神经再生轴突生长缓慢，肌肉 经常被功能上不适当的运动神经元重新支配。切割的电刺激(ES) 神经在手术修复时可明显促进再生的生长 神经营养因子介导的轴突。然而，在许多情况下，ES 可以使用，ES也会导致功能不适当的肌肉再神经支配的增加 运动神经元。运动促进了大脑和脊髓中BDNF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，跑步机训练，对周围神经轴突再生的影响。一种组合 转基因和基因敲除小鼠的研究将被用作一种新的模型系统来研究一项练习- 诱导促进再生轴突的生长是由神经营养因子介导的。通过 将跑步机训练对轴突再生的直接影响与ES产生的影响进行比较，我们将 评估所产生的促进轴突再生的作用是否相似。突触重塑是一种 三叉神经节损伤后功能恢复的关键部分，如果不干预，需要的时间比它更长 需要再生的轴突生长到足够长到肌肉。我们将比较ES和Es的效果 跑步机训练对转基因小鼠神经肌肉突触重塑时间进程的影响。因为它 通过运动神经元的内在神经回路自然激活，运动可能是一种增强 与ES相比，再生时肌肉功能不适当的神经支配较少。这个 用逆行荧光法比较四种不同肌肉靶的神经再支配的特异性。 标记方法，在未经治疗、电刺激和跑步机训练的小鼠中。锻炼有潜力 以改善导致PNS患者皮损功能恢复不佳的两个主要问题。它的 低成本、高效益的临床应用潜力巨大。这个项目提供了一个独特的 有机会为问题提供重要的答案，以加强此类临床应用的基础。