Involvement of RhoA/ROCK Signaling in Aβ-Induced Chemotaxis, Cytotoxicity and Inflammatory Response of Microglial BV2 Cells
Reactive microglia clustering around amyloid plaques in brain is a histopathological feature of Alzheimer’s disease (AD) and reflects the contribution of neuroinflammation in AD pathogenesis. β-Amyloid peptide (Aβ) has been shown to induce a range of microglial responses including chemotaxis, cytotoxicity and inflammation, but the underlying mechanism is poorly understood. Considering the fundamental role of RhoA/ROCK signaling in cell migration and its broad implication in AD and neuroinflammation, we hypothesized that RhoA/ROCK signaling might be involved in Aβ-induced microglial responses. From in vivo mouse models including APP/PS1 transgene and fibrillar Aβ stereotactic injection, we observed the elevated expression level of RhoA in reactive microglia. Through a series in vitro cell migration, cytotoxicity and biochemistry assays, we found that RhoA/ROCK signaling plays an essential role in Aβ-induced responses of microglial BV2 cells. Small molecular agents Fasudil and Y27632 showed prominent beneficial effects, which implies the therapeutic potential of RhoA/ROCK signaling inhibitors in AD treatment.
KeywordsAβ Microglial BV2 cells RhoA/ROCK signaling Chemotactic migration Cytotoxicity Inflammatory response
This work was supported by the National Natural Science Foundation of China, Grant Numbers 31671041 and 81471285.
X.Z. performed all the experiments and wrote the manuscript. P.Y. contributed to part of immunofluorescence staining, cell culture and data analysis. D.W. contributed to write and review the manuscript. Y.W., L.C. and Y.L. contributed to some of in vitro analysis. C.Z. and Y.X. designed the study, analyzed data, and wrote the manuscript. All authors reviewed and approved the final manuscript.
Compliance with Ethical Standards
Conflict of interest
The authors declare that they have no conflict of interest.
All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. This article does not contain any studies with human participants performed by any of the authors.
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