文献详情
Astrocyte scar formation aids central nervous system axon regeneration
文献类型期刊论文
作者Anderson, Mark A.[1];Burda, Joshua E.[2];Ren, Yilong[3];Ao, Yan[4];O'Shea, Timothy M.[5];Kawaguchi, Riki[6];Coppola, Giovanni[7];Khakh, Baljit S.[8];Deming, Timothy J.[9];Sofroniew, Michael V.[10]
机构
通讯作者Sofroniew, MV (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurobiol, Los Angeles, CA 90095 USA.
2016
期刊名称NATURE影响因子和分区
532
7598
页码范围195-+
增刊正刊
学科综合性期刊
收录情况SCI(E)(WOS:000374415100031)  ESI Highlycited(WOS:000374415100031)  
所属部门医院
重要成果类型ESI高被引
语言外文
ISSN0028-0836
DOI10.1038/nature17623
被引频次107
人气指数3092
浏览次数3078
基金US National Institutes of Health [NS057624, NS084030, P30 NS062691, NS060677, MH099559A, MH104069]; Dr. Miriam and Sheldon G. Adelson Medical Foundation; Wings for Life
摘要Transected axons fail to regrow in the mature central nervous system. Astrocytic 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 ablating chronic astrocytic scars all failed to result in spontaneous regrowth of transected corticospinal, sensory or serotonergic axons through severe spinal cord injury (SCI) lesions. By 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 astrocytic 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 the prevailing dogma, astrocyte scar formation aids rather than prevents central nervous system axon regeneration.
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