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- Title
Astrocytic phagocytosis contributes to demyelination after focal cortical ischemia in mice.
- Authors
Wan, Ting; Zhu, Wusheng; Zhao, Ying; Zhang, Xiaohao; Ye, Ruidong; Zuo, Meng; Xu, Pengfei; Huang, Zhenqian; Zhang, Chunni; Xie, Yi; Liu, Xinfeng
- Abstract
Ischemic stroke can cause secondary myelin damage in the white matter distal to the primary injury site. The contribution of astrocytes during secondary demyelination and the underlying mechanisms are unclear. Here, using a mouse of distal middle cerebral artery occlusion, we show that lipocalin-2 (LCN2), enriched in reactive astrocytes, expression increases in nonischemic areas of the corpus callosum upon injury. LCN2-expressing astrocytes acquire a phagocytic phenotype and are able to uptake myelin. Myelin removal is impaired in Lcn2−/− astrocytes. Inducing re-expression of truncated LCN2(Δ2–20) in astrocytes restores phagocytosis and leads to progressive demyelination in Lcn2−/− mice. Co-immunoprecipitation experiments show that LCN2 binds to low-density lipoprotein receptor-related protein 1 (LRP1) in astrocytes. Knockdown of Lrp1 reduces LCN2-induced myelin engulfment by astrocytes and reduces demyelination. Altogether, our findings suggest that LCN2/LRP1 regulates astrocyte-mediated myelin phagocytosis in a mouse model of ischemic stroke. Ischemic stroke can cause secondary demyelination. Whether phagocytic astrocytes can contribute to such demyelination is unclear. Here, the authors show that lipocalin-2 (LCN-2) expression increased in astrocytes upon injury. LCN-2 expressing astrocytes acquire a phagocytic phenotype and contribute to secondary demyelination in a mouse model of ischemic stroke.
- Subjects
DEMYELINATION; PHAGOCYTOSIS; MYELIN proteins; WHITE matter (Nerve tissue); CORPUS callosum; ISCHEMIC stroke; ASTROCYTES; OLIGODENDROGLIA
- Publication
Nature Communications, 2022, Vol 13, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-022-28777-9