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Fig. 6 | Acta Neuropathologica Communications

Fig. 6

From: Age-dependent neuroinflammation and cognitive decline in a novel Ala152Thr-Tau transgenic mouse model of PSP and AD

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: hTau40AT/mixed bkg) mice in response to expression and aggregation of hTau40AT 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: hTau40AT/mixed bkg) mice (red circles, n = 18) in comparison to Tg(Gfap-lucmixed bkg) control animals (black squares, n = 9) at 3–18 months of age. Gfap-driven luciferase activity is strongly increased in Tg(Gfap-luc: hTau40AT/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 hTau40AT. Two-way repeated measures ANOVA reveals highly significant group differences between Tg(Gfap-luc: hTau40AT/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: hTau40AT/mixed bkg) mice and Tg(Gfap-lucmixed 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. ce Progressive astrogliosis in hTau40AT mice with increasing age. c Paraffin sections of 5 to 18 months old hTau40AT and 18 months old WT mice were stained with GFAP (brown) and hematoxylin (blue). The majority of astrocytes of 18 months old hTau40AT mice shows an activated morphology (c4) compared to aged matched WT mice (c1) and younger hTau40AT mice (c2-3). d Western blot of cortical extracts demonstrates a progressive GFAP upregulation in hTau40AT 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 hTau40AT mice with increasing age compared to old WT mice. Each bar shows mean ± SEM of n = 3 animals. WT: wildtype; A152T: hTau40AT transgenic mouse strain; CA: cornu ammonis; mo: months; Scale bar: 50 μm (c1-c4)

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