Effect Of Microtubule Associated Protein Tau On Function Of Microglia

Background:Increase of microtubule associated protein tau in brains has been observed in aging and tauopathies. Besides in neurons, astrocytes and oligodendrocytes, tau deposition is observed in microglia. However, the role of tau in microglia is not illustrated.Aim:To study the effect of microtubule associated protein tau on function of microglia.Methods:In this study, immunofluorescence was used to detect and analyze the activation of cortical microglia in different ages of SD rats and C57BL/6mice. Double immunofluorescence staining was used to observe the expression of total tau (Tau46) and phosphorylated tau (AT8) in the different forms of cortical microglia in SD rats and C57BL/6mice. Human full-length2N/4R tau protein (tau40) was transiently transfected into cultured rat microglia, then we observed the effects of activity, migration, phagocytosis and secretion on microglia.Results:By immunofluorescence staining and fractal dimension analysis, we observed more microglia in cerebral cortex with lower fractal dimension values of14-month-old SD rats and12-month-old C57BL/6compared with that of4-month-old SD rats and3-month-old C57BL/6mice, indicating that overall enhanced activation of microglia Simultaneously, total tau and phosphorylated tau increased in microglia with lower fractal dimension values compared with that in microglia with higher fractal dimension values. Further studies by transient transfection of tau40or vector into the cultured rat microglia, we demonstrated that expression of tau40increased the level of Ibal, a marker of microglial activation. Furthermore, expression of tau40significantly enhanced the expression and the membranous localization of the phosphorylated tau at Ser396in microglia, it may promote tau phosphorylation through activating of ERK and GSK-3β and meanwhile suppressing of the PP2A. Finally, we also found that expression of tau40promoted microglial migration in a scratched cell model, and it stimulated phagocytosis observed by fluorescence microscope and measured by flow cytometry, and we observed that expression of tau40increased secretion of several cytokines, including interleukin (IL)-1β, IL-6, IL-10, tumor necrosis factor (TNF)-a and nitric oxide (NO) by ELISA and NO assay. Simultaneously, we observed that expression of tau40increased the secretion of tau and decreased the secretion of phosphorylated tau by dot blot.Conclusion:Our findings suggest that the expression of human full-length2N/4R tau protein (tau40) activates microglia and affects the functions, which discloses a novel role of tau in regulating microglia.