Astrocyte scar formation aids central nervous system axon regeneration.
Astrocyte scar formation aids central nervous system axon regeneration.
复制标题
星形胶质细胞疤痕形成有助于中枢神经系统轴突再生。
DOI：
10.1038/nature17623
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发表时间：
2016-04-14
期刊：
影响因子：
64.8
通讯作者：
Sofroniew MV
中科院分区：
文献类型：
--
作者：
Anderson MA;Burda JE;Ren Y;Ao Y;O'Shea TM;Kawaguchi R;Coppola G;Khakh BS;Deming TJ;Sofroniew MV
在成熟的中枢神经系统（CNS）中，横断的轴突不能再生。星形胶质细胞疤痕被广泛认为是这种失败的原因。在这里，我们在成年小鼠中使用三种基因靶向功能丧失操作，我们发现阻止星形胶质细胞瘢痕形成，减少瘢痕形成的星形胶质细胞，或删除慢性星形胶质细胞瘢痕都不能导致严重脊髓损伤（SCI）病变中横断的皮质脊髓、感觉或血清素能轴突的自发再生。与此形成鲜明对比的是，通过水凝胶库持续局部递送脊髓损伤中不存在的所需轴突特异性生长因子，加上激活生长的启动损伤，刺激了脊髓损伤中形成瘢痕的星形胶质细胞和抑制分子，刺激了强大的，依赖层粘连蛋白的感觉轴突再生。防止星形胶质细胞瘢痕形成可显著减少这种受刺激的轴突再生。RNA测序显示，脊髓损伤的星形胶质细胞和非星形胶质细胞表达多种轴突生长支持分子。我们的研究结果表明，与主流观点相反，星形胶质细胞疤痕的形成有助于而不是阻碍中枢神经系统轴突的再生。
Transected axons fail to regrow in the mature central nervous system (CNS). Astrocyte scars are widely regarded as causal in this failure. Here, using three genetically targeted loss-of-function manipulations in adult mice, we show that preventing astrocyte scar formation, attenuating scar-forming astrocytes, or deleting chronic astrocyte scars all failed to result in spontaneous regrowth of transected corticospinal, sensory or serotonergic axons through severe spinal cord injury (SCI) lesions. In striking contrast, sustained local delivery via hydrogel depots of required axon-specific growth factors not present in SCI lesions, plus growth-activating priming injuries, stimulated robust, laminin-dependent sensory axon regrowth past scar-forming astrocytes and inhibitory molecules in SCI lesions. Preventing astrocyte scar formation significantly reduced this stimulated axon regrowth. RNA sequencing revealed that astrocytes and non-astrocyte cells in SCI lesions express multiple axon-growth supporting molecules. Our findings show that contrary to prevailing dogma, astrocyte scar formation aids rather than prevents CNS axon regeneration.