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Restoring Cellular Energetics Promotes Axonal Regeneration and Functional Recovery after Spinal Cord Injury.
Cell Metabolism ( IF 29.0 ) Pub Date : 2020-03-03 , DOI: 10.1016/j.cmet.2020.02.002
Qi Han 1 , Yuxiang Xie 2 , Josue D Ordaz 1 , Andrew J Huh 1 , Ning Huang 2 , Wei Wu 1 , Naikui Liu 1 , Kelly A Chamberlain 2 , Zu-Hang Sheng 2 , Xiao-Ming Xu 1
Affiliation  

Axonal regeneration in the central nervous system (CNS) is a highly energy-demanding process. Extrinsic insults and intrinsic restrictions lead to an energy crisis in injured axons, raising the question of whether recovering energy deficits facilitates regeneration. Here, we reveal that enhancing axonal mitochondrial transport by deleting syntaphilin (Snph) recovers injury-induced mitochondrial depolarization. Using three CNS injury mouse models, we demonstrate that Snph-/- mice display enhanced corticospinal tract (CST) regeneration passing through a spinal cord lesion, accelerated regrowth of monoaminergic axons across a transection gap, and increased compensatory sprouting of uninjured CST. Notably, regenerated CST axons form functional synapses and promote motor functional recovery. Administration of the bioenergetic compound creatine boosts CST regenerative capacity in Snph-/- mice. Our study provides mechanistic insights into intrinsic regeneration failure in CNS and suggests that enhancing mitochondrial transport and cellular energetics are promising strategies to promote regeneration and functional restoration after CNS injuries.

中文翻译:

恢复细胞能量学可促进脊髓损伤后轴突再生和功能恢复。

中枢神经系统(CNS)中的轴突再生是一个高度耗能的过程。外在的侮辱和内在的限制导致受伤的轴突发生能量危机,这引发了以下问题:恢复能量不足是否促进再生。在这里,我们揭示了通过删除突触蛋白(Snph)增强轴突线粒体运输,可以恢​​复损伤引起的线粒体去极化。使用三个中枢神经系统损伤的小鼠模型,我们证明Snph-/-小鼠通过脊髓病变显示增强的皮质脊髓束(CST)再生,跨横断间隙的单胺能轴突加速再生长,并增加未损伤的CST的代偿性发芽。值得注意的是,再生的CST轴突形成功能突触并促进运动功能恢复。施用生物能化合物肌酸可增强Snph-/-小鼠的CST再生能力。我们的研究为中枢神经系统内在的再生失败提供了机械方面的见解,并表明增强线粒体运输和细胞能量学是促进中枢神经系统损伤后再生和功能恢复的有前途的策略。
更新日期:2020-03-03
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