Fig. 6

In vivo bioluminescence imaging (BLI) shows activation of astrocytes in response to aggregation of Tau. a Representative BLI signals emitted from the brains of Tg(Gfap-luc: hTau40^{AT/mixed bkg}) mice in response to expression and aggregation of hTau40^AT with increasing age (3–18 months). b Change of astrocyte activation (%) as measured by in vivo BLI of luciferase activity. Data represents mean brain bioluminescence intensities (±SEM) obtained from Tg(Gfap-luc: hTau40^{AT/mixed bkg}) mice (red circles, n = 18) in comparison to Tg(Gfap-luc^{mixed bkg}) control animals (black squares, n = 9) at 3–18 months of age. Gfap-driven luciferase activity is strongly increased in Tg(Gfap-luc: hTau40^{AT/mixed bkg}) mice from 5 months of age onwards in comparison to control groups, demonstrating an upregulation of astrocyte activation, which correlates with the aggregation of toxic hTau40^AT. Two-way repeated measures ANOVA reveals highly significant group differences between Tg(Gfap-luc: hTau40^{AT/mixed bkg}) and control groups (p < 0.0001, F_(2,199) = 33.46) and significant effect of interaction (p = 0.0001, F_(12,199) = 3.43) and time (p = 0.033, F_(6,199) = 2.33). Asterisks indicate levels of significance between Tg(Gfap-luc: hTau40^{AT/mixed bkg}) mice and Tg(Gfap-luc^{mixed bkg}) control animals as determined by post-hoc analysis. *:p < 0.05, **:p < 0.01, ***:p < 0.001, ****:p < 0.0001; mo, months of age; bkg, genetic background. c–e Progressive astrogliosis in hTau40^AT mice with increasing age. c Paraffin sections of 5 to 18 months old hTau40^AT and 18 months old WT mice were stained with GFAP (brown) and hematoxylin (blue). The majority of astrocytes of 18 months old hTau40^AT mice shows an activated morphology (c4) compared to aged matched WT mice (c1) and younger hTau40^AT mice (c2-3). d Western blot of cortical extracts demonstrates a progressive GFAP upregulation in hTau40^AT mice (time course 5, 10 and 18 months) compared to 18 months old WT mice. β-actin serves as loading control. e Densitometric analysis of western blot (d), normalized to ß-actin. The red bars indicate a progressive astrogliosis in hTau40^AT mice with increasing age compared to old WT mice. Each bar shows mean ± SEM of n = 3 animals. WT: wildtype; A152T: hTau40^AT transgenic mouse strain; CA: cornu ammonis; mo: months; Scale bar: 50 μm (c1-c4)