Department of Cell Biology, Emory University School of Medicine, 615 Michael Street, Atlanta, GA 30322, USA.
Eur J Neurosci. 2011 Jun;33(12):2265-71. doi: 10.1111/j.1460-9568.2011.07724.x. Epub 2011 May 30.
The role of neurotrophin-4/5 (NT-4/5) in the enhancement of axon regeneration in peripheral nerves produced by treadmill training was studied in mice. Common fibular nerves of animals of the H strain of thy-1-YFP mice, in which a subset of axons in peripheral nerves is marked by the presence of yellow fluorescent protein, were cut and surgically repaired using nerve grafts from non-fluorescent mice. Lengths of profiles of fluorescent regenerating axons were measured using optical sections made through whole mounts of harvested nerves. Measurements from mice that had undergone 1 h of daily treadmill training at modest speed (10 m/min) were compared with those of untrained (control) mice. Modest treadmill training resulted in fluorescent axon profiles that were nearly twice as long as controls at 1, 2 and 4 week survival times. Similar enhanced regeneration was found when cut nerves of wild type mice were repaired with grafts from NT-4/5 knockout mice or grafts made acellular by repeated freezing/thawing. No enhancement was produced by treadmill training in NT-4/5 knockout mice, irrespective of the nature of the graft used to repair the cut nerve. Much as had been observed previously for the effects of brief electrical stimulation, the effects of treadmill training on axon regeneration in cut peripheral nerves are independent of changes produced in the distal segment of the cut nerve and depend on the promotion of axon regeneration by changes in NT-4/5 expression by cells in the proximal nerve segment.
研究了神经营养因子-4/5（NT-4/5）在跑步机训练增强周围神经轴突再生中的作用，实验对象为 H 品系的 thy-1-YFP 小鼠。该品系的小鼠，其外周神经中的一部分轴突被黄色荧光蛋白标记。实验中，先切断动物的腓总神经，然后用非荧光小鼠的神经移植物进行手术修复。使用采集的神经的全切片制作光学切片，来测量荧光再生轴突的轮廓长度。将经过每天 1 小时适度速度（10 m/min）跑步机训练的小鼠的测量值与未经训练（对照）的小鼠进行比较。适度的跑步机训练导致荧光轴突的轮廓长度在 1、2 和 4 周存活时间比对照组几乎长了一倍。当用 NT-4/5 敲除小鼠的移植物或经多次冻融制成无细胞移植物修复野生型小鼠的切断神经时，也发现了类似的增强再生。在 NT-4/5 敲除小鼠中，无论使用何种移植物修复切断的神经，跑步机训练都不会产生增强效果。就像以前观察到的短暂电刺激的效果一样，跑步机训练对切断周围神经中轴突再生的影响与切断神经的远端段产生的变化无关，而是依赖于 NT-4/5 表达的变化，这些变化是由近端神经段中的细胞促进轴突再生产生的。
