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

• Published in: Molecular neurobiology Vol. 57; no. 4; pp. 1847 - 1862
• Main Authors: Sonn, Iki, Nakamura, Masaya, Renault-Mihara, Francois, Okano, Hideyuki
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.04.2020; Springer Nature B.V
• Subjects: Animals; Astrocytes; Astrocytes - metabolism; Astrocytes - pathology; Biomedical and Life Sciences; Biomedicine; Brain injury; Cell activation; Cell Biology; Cell Polarity; Chemotaxis; Integrin beta1 - metabolism; Interleukin 4; Macrophage Activation; Macrophages; Mice, Inbred C57BL; Neurobiology; Neurology; Neurosciences; Polarization; Spinal cord injuries; Spinal Cord Injuries - metabolism; Spinal Cord Injuries - pathology; Wnt protein; Wnt Signaling Pathway; Wnt3A Protein - metabolism; β-Catenin; Polarization; Reactive astrocytes; β-Catenin pathway; Glial scar; Macrophages; Spinal cord injury; Wnt
• ISSN: 0893-7648; 1559-1182
• DOI: 10.1007/s12035-019-01851-y

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.