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Functional Regeneration of the Sensory Root via Axonal Invasion.
Cell Reports ( IF 8.8 ) Pub Date : 2020-01-07 , DOI: 10.1016/j.celrep.2019.12.008
Ev L Nichols 1 , Cody J Smith 1
Affiliation  

Regeneration following spinal root avulsion is broadly unsuccessful despite the regenerative capacity of other PNS-located nerves. By combining focal laser lesioning to model root avulsion in zebrafish, time-lapse imaging, and transgenesis, we identify that regenerating DRG neurons fail to recapitulate developmental paradigms of actin-based invasion after injury. We demonstrate that inducing actin reorganization into invasive components via pharmacological and genetic approaches in the regenerating axon can rescue sensory axon spinal cord entry. Cell-autonomous induction of invasion components using constitutively active Src induces DRG axon regeneration, suggesting an intrinsic mechanism can be activated to drive regeneration. Furthermore, analyses of neuronal activity and animal behavior show restoration of sensory circuit activity and behavior upon stimulating axons to re-enter the spinal cord via invasion. Altogether, our data identify induction of invasive components as sufficient for functional sensory root regeneration after injury.

中文翻译:

通过轴突入侵的感觉根的功能再生。

尽管其他位于 PNS 的神经具有再生能力,但脊髓根撕脱后的再生普遍不成功。通过结合局部激光损伤模型来模拟斑马鱼的根部撕脱、延时成像和转基因,我们发现再生 DRG 神经元无法概括损伤后基于肌动蛋白的入侵的发育范例。我们证明,通过再生轴突中的药理学和遗传方法诱导肌动蛋白重组为侵入性成分可以挽救感觉轴突脊髓进入。使用组成型活性 Src 对入侵成分的细胞自主诱导诱导 DRG 轴突再生,表明可以激活内在机制来驱动再生。此外,对神经元活动和动物行为的分析表明,在刺激轴突通过侵入重新进入脊髓后,感觉回路活动和行为的恢复。总之,我们的数据确定侵入性成分的诱导足以在损伤后进行功能性感觉根再生。
更新日期:2020-01-07
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