Munson J B, Shelton D L, McMahon S B
Department of Neuroscience, University of Florida College of Medicine, Gainesville, Florida 32610, USA.
J Neurosci. 1997 Jan 1;17(1):470-6. doi: 10.1523/JNEUROSCI.17-01-00470.1997.
We have tested the ability of neurotrophins to reverse axotomy-induced changes in adult motor and sensory neurons, using the physiological measure of conduction velocity. Five weeks after axotomy, sensory and motor conduction velocities were greatly reduced. NT-3 at 60 microg/d, pumped directly onto the cut nerve stump, largely prevented the change in sensory fibers. Lower doses were less effective, and NT-4/5 was without effect. In contrast, both NT-3 and NT-4/5 were effective at rescuing motoneurons, with similar dose dependencies. This amelioration of physiological deficits in adult mammalian neurons suggests possible therapeutic application of neurotrophins. We have also studied the physiological effects of neurotrophin deprivation on intact peripheral neurons. After 2 weeks of sequestration of trkB ligands (BDNF and NT-4/5), motor, but not sensory, neuron conduction was significantly slowed. Sequestration of NT-3 was found to affect both motor and sensory fiber velocities but more modestly and only with higher doses of sequestering agent. These data therefore suggest that peripherally produced neurotrophins are necessary for the maintenance of normal functional properties of peripheral neurons.
我们使用传导速度这一生理学指标，测试了神经营养因子逆转成年运动和感觉神经元轴突切断诱导变化的能力。轴突切断后五周，感觉和运动传导速度大幅降低。以60微克/天的剂量将NT-3直接注入切断的神经残端，很大程度上阻止了感觉纤维的变化。较低剂量效果较差，而NT-4/5则无效。相比之下，NT-3和NT-4/5在挽救运动神经元方面均有效，且具有相似的剂量依赖性。成年哺乳动物神经元生理缺陷的这种改善表明神经营养因子可能具有治疗应用价值。我们还研究了神经营养因子剥夺对完整外周神经元的生理影响。在隔离trkB配体（BDNF和NT-4/5）两周后，运动神经元而非感觉神经元的传导显著减慢。发现隔离NT-3会影响运动和感觉纤维的速度，但影响较小，且仅在使用较高剂量的隔离剂时才会出现。因此，这些数据表明外周产生的神经营养因子对于维持外周神经元的正常功能特性是必要的。
