Publication Date:
2016-03-31
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Anderson, Mark A -- Burda, Joshua E -- Ren, Yilong -- Ao, Yan -- O'Shea, Timothy M -- Kawaguchi, Riki -- Coppola, Giovanni -- Khakh, Baljit S -- Deming, Timothy J -- Sofroniew, Michael V -- MH099559A/MH/NIMH NIH HHS/ -- MH104069/MH/NIMH NIH HHS/ -- NS057624/NS/NINDS NIH HHS/ -- NS060677/NS/NINDS NIH HHS/ -- NS084030/NS/NINDS NIH HHS/ -- P30 NS062691/NS/NINDS NIH HHS/ -- England -- Nature. 2016 Apr 14;532(7598):195-200. doi: 10.1038/nature17623. Epub 2016 Mar 30.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neurobiology, David Geffen School of Medicine, University of California, Los Angeles, California 90095-1763, USA. ; Departments of Psychiatry and Neurology, David Geffen School of Medicine, University of California, Los Angeles, California 90095-1761, USA. ; Department of Physiology, David Geffen School of Medicine, University of California, Los Angeles, California 90095-1751, USA. ; Departments of Bioengineering, Chemistry and Biochemistry, University of California Los Angeles, Los Angeles, California 90095-1600, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27027288" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Astrocytes/*pathology
;
Axons/*physiology
;
Central Nervous System/cytology/*pathology/*physiology
;
Chondroitin Sulfate Proteoglycans/biosynthesis
;
Cicatrix/*pathology/prevention & control
;
Female
;
Genomics
;
Mice
;
*Models, Biological
;
*Nerve Regeneration
;
Reproducibility of Results
;
Spinal Cord Injuries/genetics/pathology
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
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