Promotion of corticospinal tract growth by KLF6 requires an injury stimulus and occurs within four weeks of treatment.
Promotion of corticospinal tract growth by KLF6 requires an injury stimulus and occurs within four weeks of treatment.
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DOI：
10.1016/j.expneurol.2021.113644
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发表时间：
2021-05
影响因子：
5.3
通讯作者：
Blackmore MG
中科院分区：
文献类型：
--
作者：
Kramer AA;Olson GM;Chakraborty A;Blackmore MG
部分脊髓损伤后，皮质脊髓束（CST）轴突代偿发芽的能力有限，可能限制功能恢复。发育表达的转录因子kr<s:1> ppel样因子6 （KLF6）的强制表达可以促进成年CST神经元的轴突发芽。在这里，我们使用成年小鼠的损伤锥体切开术模型，证实了KLF6在皮质脊髓束神经元中促进发芽的特性，并表明这种作用依赖于损伤刺激。此外，我们探索了klf6触发的CST轴突发芽的时间过程，并在治疗四周内证明了生长的显著增强。最后，我们测试了klf6诱导的发芽是否伴随着前肢功能的改善，无论是单独还是与强化康复相结合。我们发现，无论康复训练如何，尽管皮质脊髓束轴突有强大的跨中线芽生，但用KLF6治疗，无论是在改良的阶梯穿越任务还是在捡回颗粒任务中，前肢功能都没有显著改善。这些数据阐明了KLF6促生长特性的重要细节，并表明需要额外的干预或进一步优化才能将轴突生长的改善转化为功能增益。
Axons in the corticospinal tract (CST) display a limited capacity for compensatory sprouting after partial spinal injuries, potentially limiting functional recovery. Forced expression of a developmentally expressed transcription factor, Krüppel-like factor 6 (KLF6), enhances axon sprouting by adult CST neurons. Here, using a pyramidotomy model of injury in adult mice, we confirm KLF6’s pro-sprouting properties in spared corticospinal tract neurons and show that this effect depends on an injury stimulus. In addition, we probed the time course of KLF6-triggered sprouting of CST axons and demonstrate a significant enhancement of growth within four weeks of treatment. Finally, we tested whether KLF6-induced sprouting was accompanied by improvements in forelimb function, either singly or when combined with intensive rehabilitation. We found that regardless of rehabilitative training, and despite robust cross-midline sprouting by corticospinal tract axons, treatment with KLF6 produced no significant improvement in forelimb function on either a modified ladder-crossing task or a pellet-retrieval task. These data clarify important details of KLF6’s pro-growth properties and indicate that additional interventions or further optimization will be needed to translate this improvement in axon growth into functional gains.
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影响因子：
3.5
作者：
Carmel JB;Martin JH
通讯作者：
Martin JH
影响因子：
3.5
作者：
Blackmore, Murray G.;Moore, Darcie L.;Smith, Robin P.;Goldberg, Jeffrey L.;Bixby, John L.;Lemmon, Vance P.
通讯作者：
Lemmon, Vance P.
影响因子：
4.2
作者：
Lee, Hyun Joon;Bian, Shan;Schachner, Melitta
通讯作者：
Schachner, Melitta
DOI：
10.1016/j.apmr.2016.09.124
发表时间：
2017-06-01
影响因子：
4.3
作者：
Holtz, Kaila A.;Lipson, Rachel;Mills, Patricia B.
通讯作者：
Mills, Patricia B.
影响因子：
3.7
作者：
Lang C;Guo X;Kerschensteiner M;Bareyre FM
通讯作者：
Bareyre FM