Polarization of Reactive Astrocytes in Response to Spinal Cord Injury is Enhanced by M2 Macrophage–Mediated Activation of Wnt/β-Catenin Pathway

Iki Sonn, Masaya Nakamura, Francois Renault-Mihara, Hideyuki Okano

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Understanding the mechanisms of glial scar formation by reactive astrocytes is crucial for elaborating a therapeutic strategy to brain and spinal cord injury. However, the extrinsic mechanisms that drive the polarization of reactive astrocytes, the first step in glial scar formation, remain poorly understood. Here, using an in vitro chemotaxis assay as an experimental model for polarization, we observed that Il4-M2 macrophages are stronger inducers of reactive astrocytes’ polarization, compared to naive or M1 macrophages. Then, we showed that both β1-integrin and Wnt/β-catenin pathways in astrocytes are required for this polarization in vitro and in vivo after spinal cord crush injury in mice. These findings provide molecular targets for manipulating the polarization of reactive astrocytes in order to potentially enhance the healing of SCI lesions.

Original languageEnglish
Pages (from-to)1847-1862
Number of pages16
JournalMolecular Neurobiology
Volume57
Issue number4
DOIs
Publication statusPublished - 2020 Apr 1

Keywords

  • Glial scar
  • Macrophages
  • Polarization
  • Reactive astrocytes
  • Spinal cord injury
  • Wnt
  • β-Catenin pathway

ASJC Scopus subject areas

  • Neurology
  • Cellular and Molecular Neuroscience

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