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Stroke subtype-dependent synapse elimination by reactive gliosis in mice

Author

Listed:
  • Xiaojing Shi

    (Shanghai Jiao Tong University)

  • Longlong Luo

    (Shanghai Jiao Tong University
    Karolinska Institute)

  • Jixian Wang

    (Shanghai Jiao Tong University)

  • Hui Shen

    (Shanghai Jiao Tong University)

  • Yongfang Li

    (Shanghai Jiao Tong University)

  • Muyassar Mamtilahun

    (Shanghai Jiao Tong University)

  • Chang Liu

    (Shanghai Jiao Tong University)

  • Rubing Shi

    (Shanghai Jiao Tong University)

  • Joon-Hyuk Lee

    (Korea Advanced Institute of Science and Technology)

  • Hengli Tian

    (Shanghai Jiao Tong University)

  • Zhijun Zhang

    (Shanghai Jiao Tong University)

  • Yongting Wang

    (Shanghai Jiao Tong University)

  • Won-Suk Chung

    (Korea Advanced Institute of Science and Technology)

  • Yaohui Tang

    (Shanghai Jiao Tong University)

  • Guo-Yuan Yang

    (Shanghai Jiao Tong University
    Shanghai Jiao Tong University)

Abstract

The pathological role of reactive gliosis in CNS repair remains controversial. In this study, using murine ischemic and hemorrhagic stroke models, we demonstrated that microglia/macrophages and astrocytes are differentially involved in engulfing synapses in the reactive gliosis region. By specifically deleting MEGF10 and MERTK phagocytic receptors, we determined that inhibiting phagocytosis of microglia/macrophages or astrocytes in ischemic stroke improved neurobehavioral outcomes and attenuated brain damage. In hemorrhagic stroke, inhibiting phagocytosis of microglia/macrophages but not astrocytes improved neurobehavioral outcomes. Single-cell RNA sequencing revealed that phagocytosis related biological processes and pathways were downregulated in astrocytes of the hemorrhagic brain compared to the ischemic brain. Together, these findings suggest that reactive microgliosis and astrogliosis play individual roles in mediating synapse engulfment in pathologically distinct murine stroke models and preventing this process could rescue synapse loss.

Suggested Citation

  • 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.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-27248-x
    DOI: 10.1038/s41467-021-27248-x
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    References listed on IDEAS

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    1. 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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