期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 112, 期 51, 页码 15556-15561出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1516779112
关键词
Alzheimer's disease; astrocyte; spatial analysis; sulforhodamine 101; two-photon
资金
- Ministerio de Educacion, Cultura y Deporte [PR2011-0511]
- Ministerio de Economia y Competitividad [BFU2012-38844]
- NIH [EB000768, S10 RR025645, P50 AG005134, AG021133]
- National Science Foundation [CMMI 1125290, PHY-1444389, PHY-0855161, PHY-1505000]
- Direct For Mathematical & Physical Scien [1504804] Funding Source: National Science Foundation
- Direct For Mathematical & Physical Scien
- Division Of Physics [1505000] Funding Source: National Science Foundation
- Division Of Physics [1504804] Funding Source: National Science Foundation
- ICREA Funding Source: Custom
Although the clustering of GFAP immunopositive astrocytes around amyloid-beta plaques in Alzheimer's disease has led to the widespread assumption that plaques attract astrocytes, recent studies suggest that astrocytes stay put in injury. Here we reexamine astrocyte migration to plaques, using quantitative spatial analysis and computer modeling to investigate the topology of astrocytes in 3D images obtained by two-photon microscopy of living APP/PS1 mice and WT littermates. In WT mice, cortical astrocyte topology fits a model in which a liquid of hard spheres exclude each other in a confined space. Plaques do not disturb this arrangement except at very large plaque loads, but, locally, cause subtle outward shifts of the astrocytes located in three tiers around plaques. These data suggest that astrocytes respond to plaque-induced neuropil injury primarily by changing phenotype, and hence function, rather than location.
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