Astrocyte scar formation aids central nervous system axon regeneration

Mark A. Anderson, Joshua E. Burda, Yilong Ren, Yan Ao, Timothy M. O’Shea, Riki Kawaguchi, Giovanni Coppola, Baljit S. Khakh, Timothy J. Deming and Michael V. Sofroniew ()
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Mark A. Anderson: David Geffen School of Medicine, University of California
Joshua E. Burda: David Geffen School of Medicine, University of California
Yilong Ren: David Geffen School of Medicine, University of California
Yan Ao: David Geffen School of Medicine, University of California
Timothy M. O’Shea: David Geffen School of Medicine, University of California
Riki Kawaguchi: David Geffen School of Medicine, University of California
Giovanni Coppola: David Geffen School of Medicine, University of California
Baljit S. Khakh: David Geffen School of Medicine, University of California
Timothy J. Deming: Chemistry and Biochemistry, University of California Los Angeles
Michael V. Sofroniew: David Geffen School of Medicine, University of California

Nature, 2016, vol. 532, issue 7598, 195-200

Abstract: Abstract 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.

Date: 2016
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DOI: 10.1038/nature17623

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