Enriched conditioning expands the regenerative ability of sensory neurons after spinal cord injury via neuronal intrinsic redox signaling.
Enriched conditioning expands the regenerative ability of sensory neurons after spinal cord injury via neuronal intrinsic redox signaling.
复制标题
DOI：
10.1038/s41467-020-20179-z
复制
发表时间：
2020-12-21
影响因子：
16.6
通讯作者：
Di Giovanni S
中科院分区：
文献类型：
--
作者：
De Virgiliis F;Hutson TH;Palmisano I;Amachree S;Miao J;Zhou L;Todorova R;Thompson R;Danzi MC;Lemmon VP;Bixby JL;Wittig I;Shah AM;Di Giovanni S
克服限制轴突再生能力，限制中枢神经系统损伤后的功能修复仍然是一个挑战。在这里，我们报告了一种被我们称为丰富的条件反射的再生范式，它结合了环境丰富(EE)和脊髓损伤(SCI)之前的条件坐骨神经切断。与EE或单独的条件性损伤相比，丰富的条件反射显著增加背根神经节(DRG)感觉神经元的再生能力，推动轴突生长远远超出脊髓损伤部位。我们从机制上证实，丰富的条件反射依赖于独特的神经元内在信号轴PKC-STAT3-NADPH氧化酶2(NOX2)，增强了DRG中的氧化还原信号，如氧化还原蛋白质组学所示。最后，NOX2条件性缺失或过表达分别阻断或表型复制增强脊髓损伤后条件性轴突再生，促进功能恢复。这些研究提供了一个驱动感觉神经元再生能力的范例，为机械和治疗的发现提供了一个潜在的氧化还原依赖的再生模型。已有研究表明，预适应损伤或环境丰富可以促进轴突再生。在这里，作者表明，环境丰富，与预适应损伤相结合，通过氧化还原信号依赖机制促进再生。
Overcoming the restricted axonal regenerative ability that limits functional repair following a central nervous system injury remains a challenge. Here we report a regenerative paradigm that we call enriched conditioning, which combines environmental enrichment (EE) followed by a conditioning sciatic nerve axotomy that precedes a spinal cord injury (SCI). Enriched conditioning significantly increases the regenerative ability of dorsal root ganglia (DRG) sensory neurons compared to EE or a conditioning injury alone, propelling axon growth well beyond the spinal injury site. Mechanistically, we established that enriched conditioning relies on the unique neuronal intrinsic signaling axis PKC-STAT3-NADPH oxidase 2 (NOX2), enhancing redox signaling as shown by redox proteomics in DRG. Finally, NOX2 conditional deletion or overexpression respectively blocked or phenocopied enriched conditioning-dependent axon regeneration after SCI leading to improved functional recovery. These studies provide a paradigm that drives the regenerative ability of sensory neurons offering a potential redox-dependent regenerative model for mechanistic and therapeutic discoveries. Pre conditioning injury or environmental enrichment have been shown to promote axon regeneration. Here the authors show that environmental enrichment, combined with preconditioning injury promotes regeneration via a redox signalling dependent mechanism.
登录
查看更多内容
脊髓刺激必须保留本体感受，以使脊髓损伤的人类运动。
影响因子：
25
作者：
Formento E;Minassian K;Wagner F;Mignardot JB;Le Goff-Mignardot CG;Rowald A;Bloch J;Micera S;Capogrosso M;Courtine G
通讯作者：
Courtine G
影响因子：
5.7
作者：
Cho Y;Cavalli V
通讯作者：
Cavalli V
影响因子：
64.5
作者：
Cho Y;Sloutsky R;Naegle KM;Cavalli V
通讯作者：
Cavalli V
影响因子：
6.1
作者：
Al-Ali H;Bixby JL;Lemmon VP
通讯作者：
Lemmon VP
DOI：
10.1177/1073858408331372
发表时间：
2009-04
期刊：
The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry
影响因子：
--
作者：
Darian-Smith C
通讯作者：
Darian-Smith C