Cooperative roles of BDNF expression in neurons and Schwann cells are modulated by exercise to facilitate nerve regeneration.
Cooperative roles of BDNF expression in neurons and Schwann cells are modulated by exercise to facilitate nerve regeneration.
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DOI：
10.1523/jneurosci.1411-11.2012
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发表时间：
2012-04-04
期刊：
影响因子：
--
通讯作者：
English AW
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文献类型：
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作者：
Wilhelm JC;Xu M;Cucoranu D;Chmielewski S;Holmes T;Lau KS;Bassell GJ;English AW
周围神经损伤后，神经营养因子在损伤轴突的再生中起关键作用，运动可以增强损伤轴突的再生，但神经元和雪旺细胞所起的不同作用尚不清楚。在这项研究中，我们评估了神经营养因子，脑源性神经营养因子，在神经元和雪旺细胞中，对损伤后周围轴突再生的需求。切断THY-1-YFP-H小鼠双侧腓总神经或胫神经，并用雪旺细胞(BDNF-/-)或野生型小鼠(WT)中缺失BDNF的转基因小鼠的同一神经移植修复。修复后2周，BDNF-/-移植物的轴突再生明显少于WT移植物，强调了雪旺细胞BDNF的重要性。无论神经移植物的BDNF含量如何，横断后的跑步机训练都能促进神经再生。我们进一步测试了这样一个假设，即训练诱导的神经元中BDNF的增加允许再生轴突克服再生路径中细胞中缺乏BDNF表达的问题。将YFP+神经元(SLICK)中缺乏BDNF的小鼠的神经切断，用BDNF-/-和WT神经修复。缺少脑源性神经营养因子的光滑轴突不能再生为缺少雪旺细胞神经营养因子的移植物。如果神经元也缺乏BDNF，则跑步机训练不能挽救BDNF-/-移植物的再生。因此，雪旺细胞和神经元来源的BDNF对于切断的周围神经的轴突再生都是重要的。
After peripheral nerve injury, neurotrophins play a key role in the regeneration of damaged axons which can be augmented by exercise, although the distinct roles played by neurons and Schwann cells are unclear. In this study, we evaluated the requirement for the neurotrophin, brain derived neurotrophic factor (BDNF), in neurons and Schwann cells, for the regeneration of peripheral axons after injury. Common fibular or tibial nerves in thy-1-YFP-H mice were cut bilaterally and repaired using a graft of the same nerve from transgenic mice lacking BDNF in Schwann cells (BDNF-/-) or wild-type mice (WT). Two weeks post-repair, axonal regeneration into BDNF-/- grafts were markedly less than WT grafts, emphasizing the importance of Schwann cell BDNF. Nerve regeneration was enhanced by treadmill training post-transection, regardless of the BDNF content of the nerve graft. We further tested the hypothesis that training-induced increases in BDNF in neurons allow regenerating axons to overcome a lack of BDNF expression in cells in the pathway through which they regenerate. Nerves in mice lacking BDNF in YFP+ neurons (SLICK) were cut and repaired with BDNF-/- and WT nerves. SLICK axons lacking BDNF did not regenerate into grafts lacking Schwann cell BDNF. Treadmill training could not rescue the regeneration into BDNF-/- grafts if the neurons also lacked BDNF. Both Schwann cell- and neuron-derived BDNF are thus important for axon regeneration in cut peripheral nerves.