IDEAS home Printed from https://ideas.repec.org/a/nat/nature/v532y2016i7598d10.1038_nature17623.html
   My bibliography  Save this article

Astrocyte scar formation aids central nervous system axon regeneration

Author

Listed:
  • Mark A. Anderson

    (David Geffen School of Medicine, University of California
    †Present addresses: School of Life Sciences, Swiss Federal Institute of Technology (EPFL), SV BMI UPCourtine, Station 19, CH-1015 Lausanne, Switzerland (M.A.A); Department of Spine Surgery, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China (Y.R.).)

  • Joshua E. Burda

    (David Geffen School of Medicine, University of California)

  • Yilong Ren

    (David Geffen School of Medicine, University of California
    †Present addresses: School of Life Sciences, Swiss Federal Institute of Technology (EPFL), SV BMI UPCourtine, Station 19, CH-1015 Lausanne, Switzerland (M.A.A); Department of Spine Surgery, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China (Y.R.).)

  • 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)

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.

Suggested Citation

  • Mark A. Anderson & Joshua E. Burda & Yilong Ren & Yan Ao & Timothy M. O’Shea & Riki Kawaguchi & Giovanni Coppola & Baljit S. Khakh & Timothy J. Deming & Michael V. Sofroniew, 2016. "Astrocyte scar formation aids central nervous system axon regeneration," Nature, Nature, vol. 532(7598), pages 195-200, April.
    • Handle: RePEc:nat:nature:v:532:y:2016:i:7598:d:10.1038_nature17623
    DOI: 10.1038/nature17623
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/nature17623
    File Function: Abstract
    Download Restriction: Access to the full text of the articles in this series is restricted.
    File URL: https://libkey.io/10.1038/nature17623?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    As the access to this document is restricted, you may want to search for a different version of it.

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Xiaojing Shi & Longlong Luo & Jixian Wang & Hui Shen & Yongfang Li & Muyassar Mamtilahun & Chang Liu & Rubing Shi & Joon-Hyuk Lee & Hengli Tian & Zhijun Zhang & Yongting Wang & Won-Suk Chung & Yaohui , 2021. "Stroke subtype-dependent synapse elimination by reactive gliosis in mice," Nature Communications, Nature, vol. 12(1), pages 1-19, December.
    2. Valentina Cigliola & Adam Shoffner & Nutishia Lee & Jianhong Ou & Trevor J. Gonzalez & Jiaul Hoque & Clayton J. Becker & Yanchao Han & Grace Shen & Timothy D. Faw & Muhammad M. Abd-El-Barr & Shyni Var, 2023. "Spinal cord repair is modulated by the neurogenic factor Hb-egf under direction of a regeneration-associated enhancer," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    3. Wenlu Li & Emiri T. Mandeville & Violeta Durán-Laforet & Norito Fukuda & Zhanyang Yu & Yi Zheng & Aaron Held & Ji-Hyun Park & Takafumi Nakano & Masayoshi Tanaka & Jingfei Shi & Elga Esposito & Wanting, 2022. "Endothelial cells regulate astrocyte to neural progenitor cell trans-differentiation in a mouse model of stroke," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    4. Wei Li & Jian Chen & Shujie Zhao & Tianhe Huang & Huiyan Ying & Claudia Trujillo & Giuseppina Molinaro & Zheng Zhou & Tao Jiang & Wei Liu & Linwei Li & Yuancheng Bai & Peng Quan & Yaping Ding & Jouni , 2022. "High drug-loaded microspheres enabled by controlled in-droplet precipitation promote functional recovery after spinal cord injury," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    5. Yuyan Cheng & Yuqin Yin & Alice Zhang & Alexander M. Bernstein & Riki Kawaguchi & Kun Gao & Kyra Potter & Hui-Ya Gilbert & Yan Ao & Jing Ou & Catherine J. Fricano-Kugler & Jeffrey L. Goldberg & Zhigan, 2022. "Transcription factor network analysis identifies REST/NRSF as an intrinsic regulator of CNS regeneration in mice," Nature Communications, Nature, vol. 13(1), pages 1-22, December.
    6. T. M. O’Shea & Y. Ao & S. Wang & A. L. Wollenberg & J. H. Kim & R. A. Ramos Espinoza & A. Czechanski & L. G. Reinholdt & T. J. Deming & M. V. Sofroniew, 2022. "Lesion environments direct transplanted neural progenitors towards a wound repair astroglial phenotype in mice," Nature Communications, Nature, vol. 13(1), pages 1-22, December.
    7. Christina Koupourtidou & Veronika Schwarz & Hananeh Aliee & Simon Frerich & Judith Fischer-Sternjak & Riccardo Bocchi & Tatiana Simon-Ebert & Xianshu Bai & Swetlana Sirko & Frank Kirchhoff & Martin Di, 2024. "Shared inflammatory glial cell signature after stab wound injury, revealed by spatial, temporal, and cell-type-specific profiling of the murine cerebral cortex," Nature Communications, Nature, vol. 15(1), pages 1-22, December.
    8. Floriane Bretheau & Adrian Castellanos-Molina & Dominic Bélanger & Maxime Kusik & Benoit Mailhot & Ana Boisvert & Nicolas Vallières & Martine Lessard & Matthias Gunzer & Xiaoyu Liu & Éric Boilard & Ni, 2022. "The alarmin interleukin-1α triggers secondary degeneration through reactive astrocytes and endothelium after spinal cord injury," Nature Communications, Nature, vol. 13(1), pages 1-22, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:nature:v:532:y:2016:i:7598:d:10.1038_nature17623. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.