Optogenetically enhanced axon regeneration: motor versus sensory neuron-specific stimulation
Optogenetically enhanced axon regeneration: motor versus sensory neuron-specific stimulation
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DOI：
10.1111/ejn.13836
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发表时间：
2018-02-01
影响因子：
3.4
通讯作者：
English, Arthur W.
中科院分区：
文献类型：
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作者：
Ward, Patricia J.;Clanton, Scott L., II;English, Arthur W.
受损周围神经中短暂的神经元激活对于增强运动轴突再生来说是必要且充分的，并且这种效应是激活的运动神经元所特有的。目前尚不清楚感觉神经元是否以类似的方式对周围轴突切除术后的神经元激活做出反应。此外，尚不清楚轴突再生随着神经元活动的增加而增强在多大程度上依赖于脊髓回路内的反射性相互作用。我们使用小鼠遗传学和光学工具来评估系统特异性神经元激活的精度和选择性，以增强混合神经中的轴突再生。我们在表达光敏阳离子通道视紫红质通道（ChR2）的两种不同小鼠模型中评估了感觉和运动轴突再生。我们使用光刺激结合坐骨神经的横断和修复来选择性地激活感觉或运动轴突。无论基因型如何，在系统特异性光学治疗后，轴突成功再生的 ChR2 阳性神经元数量更多，而对 ChR2 阴性神经元（无论是运动神经元还是感觉神经元）的数量没有影响。我们的结论是，急性系统特异性神经元激活足以增强运动和感觉轴突再生。这种再生增强作用可能是细胞自主的。
Brief neuronal activation in injured peripheral nerves is both necessary and sufficient to enhance motor axon regeneration, and this effect is specific to the activated motoneurons. It is less clear whether sensory neurons respond in a similar manner to neuronal activation following peripheral axotomy. Further, it is unknown to what extent enhancement of axon regeneration with increased neuronal activity relies on a reflexive interaction within the spinal circuitry. We used mouse genetics and optical tools to evaluatethe precision and selectivity of system-specific neuronal activation to enhance axon regeneration in a mixed nerve. We evaluated sensory and motor axon regeneration in two different mouse models expressing the light-sensitive cation channel, channelrhodopsin (ChR2). We selectively activated either sensory or motor axons using light stimulation combined with transection and repair of the sciatic nerve. Regardless of genotype, the number of ChR2-positive neurons whose axons had regenerated successfully was greater following system-specific optical treatment, with no effect on the number of ChR2-negative neurons (whether motor or sensory neurons). We conclude that acute system-specific neuronal activation is sufficient to enhance both motor and sensory axon regeneration. This regeneration-enhancing effect is likely cell autonomous.