ENDOGENOUS MODULATION OF TRKB SIGNALING BY TREADMILL EXERCISE AFTER PERIPHERAL NERVE INJURY
ENDOGENOUS MODULATION OF TRKB SIGNALING BY TREADMILL EXERCISE AFTER PERIPHERAL NERVE INJURY
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DOI：
10.1016/j.neuroscience.2016.10.057
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发表时间：
2017-01-06
期刊：
影响因子：
3.3
通讯作者：
Udina, Esther
中科院分区：
文献类型：
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作者：
Arbat-Plana, Ariadna;Cobianchi, Stefano;Udina, Esther
周围神经损伤后，损伤远端的横断纤维与神经小体断开。这会导致靶神经的丧失，但也会使轴突切断的运动神经元的中央突触大量剥离，扰乱脊髓回路。即使在轴突再生成功的情况下，非特异性靶神经的再支配和脊髓回路的有限重建也会损害功能恢复。因此，在神经损伤后保留脊髓回路的策略可能会改善功能结果。早期跑步机运动形式的活动依赖疗法减少了突触的剥离，主要是兴奋性突触，以及轴突切断后运动神经元上神经周网络(PNN)的解体。这些效应背后的机制尚不清楚，尽管运动的好处通常被归因于神经营养因子脑源性神经营养因子(BDNF)的增加。本研究应用原肌球蛋白相关激酶(TrkB)激动剂和拮抗剂对坐骨神经损伤大鼠进行治疗，以阐明BDNF的作用。跑台运动诱导的轴突切断运动神经元突触的维持部分依赖于TrkB的激活。TrkB激动剂在低剂量而不是高剂量治疗可以阻止兴奋性谷氨酸能突触的减少，并且两种剂量都增加了抑制性突触的密度。TrkB的失活只抵消了运动在神经损伤后所产生的一些积极影响，例如维持运动神经元周围的兴奋性突触。因此，与药物调节TrkB通路相比，特定的体育锻炼方案是减轻运动神经元在轴突切断后所遭受的改变的更好的策略。(C)2016年IBRO。爱思唯尔有限公司出版。保留所有权利。
After peripheral nerve injury, transected fibers distal to the lesion are disconnected from the neuronal body. This results in target denervation but also massive stripping of the central synapses of axotomized motoneurons, disrupting spinal circuits. Even when axonal regeneration is successful, the non-specific target reinnervation and the limited rebuilding of spinal circuits impair functional recovery. Therefore, strategies aimed to preserve spinal circuits after nerve lesions may improve the functional outcome. Activity-dependent therapy in the form of early treadmill running reduces synaptic stripping, mainly of excitatory synapses, and the disorganization of perineuronal nets (PNNs) on axotomized motoneurons. The mechanism underlying these effects remains unknown, although the benefits of exercise are often attributed to an increase in the neurotrophin brain-derived neurotrophic factor (BDNF). In this study, tropomyosin-related kinase (TrkB) agonist and antagonist were administered to rats subjected to sciatic nerve injury in order to shed light on the role of BDNF. The maintenance of synapses on axotomized motoneurons induced by treadmill running was partially dependent on TrkB activation. Treatment with the TrkB agonist at a low dose, but not at a high dose, prevented the decrease of excitatory glutamatergic synapses, and both doses increased the density of inhibitory synapses. TrkB inactivation counteracted only some of the positive effects exerted by exercise after nerve injury, such as maintenance of excitatory synapses surrounding motoneurons. Therefore, specific regimes of physical exercise are a better strategy to attenuate the alterations that motoneurons suffer after axotomy than pharmacological modulation of the TrkB pathway. (C) 2016 IBRO. Published by Elsevier Ltd. All rights reserved.