Secretome analyses of Aβ(1-42) stimulated hippocampal astrocytes reveal that CXCL10 is involved in astrocyte migration

Abstract

Amyloid-beta (Aβ) aggregation plays an important role in the development of Alzheimer's disease (AD). In the AD brain, amyloid plaques are surrounded by reactive astrocytes, and many essential functions of astrocytes have been reported to be mediated by protein secretion. However, the roles of activated astrocytes in AD progression are under intense debate. To provide an in-depth view of the secretomes of activated astrocytes, we present in this study a quantitative profile of rat hippocampal astrocyte secretomes at multiple time points after both brief and sustained Aβ(1-42) stimulation. Using SILAC labeling and LC-MS/MS analyses, we identified 19 up-regulated secreted proteins after Aβ(1-42) treatment. These differentially expressed proteins have been suggested to be involved in key aspects of biological processes, such as cell recruitment, Aβ clearance, and regulation of neurogenesis. Particularly, we validated the role played by CXCL10 in promoting astrocyte aggregation around amyloid plagues through in vitro cell migration analysis. This research provides global, quantitative profiling of astrocyte secretomes produced on Aβ stimulation and hence provides a detailed molecular basis for the relationship between amyloid plaques and astrocyte aggregation; the findings thus have important implications for further investigations into AD development and therapy.