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A neuroprotective astrocyte state is induced by neuronal signal EphB1 but fails in ALS models

Author

Listed:
  • Giulia E. Tyzack

    (University of Cambridge, E.D. Adrian Building
    University College London)

  • Claire E. Hall

    (University College London)

  • Christopher R. Sibley

    (Burlington Danes Building Du Cane Road)

  • Tomasz Cymes

    (University of Cambridge, E.D. Adrian Building)

  • Serhiy Forostyak

    (Department of Neuroscience)

  • Giulia Carlino

    (University College London)

  • Ione F. Meyer

    (UCL Institute of Neurology, University College London)

  • Giampietro Schiavo

    (UCL Institute of Neurology, University College London
    University College London)

  • Su-Chun Zhang

    (University of Wisconsin)

  • George M. Gibbons

    (University of Cambridge, E.D. Adrian Building)

  • Jia Newcombe

    (University College London)

  • Rickie Patani

    (University College London
    The Francis Crick Institute)

  • András Lakatos

    (University of Cambridge, E.D. Adrian Building
    Cambridge University Hospitals)

Abstract

Astrocyte responses to neuronal injury may be beneficial or detrimental to neuronal recovery, but the mechanisms that determine these different responses are poorly understood. Here we show that ephrin type-B receptor 1 (EphB1) is upregulated in injured motor neurons, which in turn can activate astrocytes through ephrin-B1-mediated stimulation of signal transducer and activator of transcription-3 (STAT3). Transcriptional analysis shows that EphB1 induces a protective and anti-inflammatory signature in astrocytes, partially linked to the STAT3 network. This is distinct from the response evoked by interleukin (IL)-6 that is known to induce both pro inflammatory and anti-inflammatory processes. Finally, we demonstrate that the EphB1–ephrin-B1 pathway is disrupted in human stem cell derived astrocyte and mouse models of amyotrophic lateral sclerosis (ALS). Our work identifies an early neuronal help-me signal that activates a neuroprotective astrocytic response, which fails in ALS, and therefore represents an attractive therapeutic target.

Suggested Citation

  • Giulia E. Tyzack & Claire E. Hall & Christopher R. Sibley & Tomasz Cymes & Serhiy Forostyak & Giulia Carlino & Ione F. Meyer & Giampietro Schiavo & Su-Chun Zhang & George M. Gibbons & Jia Newcombe & R, 2017. "A neuroprotective astrocyte state is induced by neuronal signal EphB1 but fails in ALS models," Nature Communications, Nature, vol. 8(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-01283-z
    DOI: 10.1038/s41467-017-01283-z
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    Cited by:

    1. 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.
    2. 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.

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