Live imaging of astrocyte responses to acute injury reveals selective juxtavascular proliferation

被引:317
作者
Bardehle, Sophia [1 ,2 ]
Krueger, Martin [3 ]
Buggenthin, Felix [4 ,5 ]
Schwausch, Julia [2 ]
Ninkovic, Jovica [2 ]
Clevers, Hans [6 ,7 ]
Snippert, Hugo J. [6 ,7 ]
Theis, Fabian J. [4 ,5 ]
Meyer-Luehmann, Melanie [8 ,9 ]
Bechmann, Ingo [3 ]
Dimou, Leda [1 ,2 ]
Goetz, Magdalena [1 ,2 ,10 ]
机构
[1] Univ Munich, Inst Physiol, D-80539 Munich, Germany
[2] Helmholtz Zentrum Munich, Inst Stem Cell Res, Neuherberg, Germany
[3] Univ Leipzig, Inst Anat, D-04109 Leipzig, Germany
[4] Helmholtz Zentrum Munich, Inst Bioinformat & Syst Biol, Neuherberg, Germany
[5] Tech Univ Munich, Dept Math, D-80290 Munich, Germany
[6] Koninklijke Nederlandse Akad Wetenschappen, Hubrecht Inst, Connecticut Utrecht, Netherlands
[7] Univ Med Ctr Utrecht, Connecticut Utrecht, Netherlands
[8] Univ Munich, Dept Biochem, Adolf Butenandt Inst, Munich, Germany
[9] Univ Freiburg, Dept Neurol, Neuroctr, Freiburg, Germany
[10] Munich Cluster Syst Neurol SyNergy, Munich, Germany
基金
欧洲研究理事会;
关键词
IN-VITRO; MOUSE MODEL; RHO-GTPASE; GLIA; CELLS; CDC42; TOOL; REGENERATION; EXPRESSION; DELETION;
D O I
10.1038/nn.3371
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Astrocytes are thought to have important roles after brain injury, but their behavior has largely been inferred from postmortem analysis. To examine the mechanisms that recruit astrocytes to sites of injury, we used in vivo two-photon laser-scanning microscopy to follow the response of GFP-labeled astrocytes in the adult mouse cerebral cortex over several weeks after acute injury. Live imaging revealed a marked heterogeneity in the reaction of individual astrocytes, with one subset retaining their initial morphology, another directing their processes toward the lesion, and a distinct subset located at juxtavascular sites proliferating. Although no astrocytes actively migrated toward the injury site, selective proliferation of juxtavascular astrocytes was observed after the introduction of a lesion and was still the case, even though the extent was reduced, after astrocyte-specific deletion of the RhoGTPase Cdc42. Thus, astrocyte recruitment after injury relies solely on proliferation in a specific niche.
引用
收藏
页码:580 / +
页数:9
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