Fig. 5

Activation of microglia and astrocytes in hTau40^AT mice. a Brain sections of hTau40^AT and WT mice stained with antibodies against GFAP (a1-4), S100b (a5-6), Iba1 (a7-8), CD45 (a9-10), CD11b (a11-12), IL1ß (a13-14) and TLR2 (a15-16) and partly counterstained with hematoxylin (blue). Prominent astrogliosis detected by GFAP and S100b occurs particularly inside the hippocampus formation, demonstrated by higher numbers of reactive astrocytes in hilus (a2), CA3 (a4) and CA1 (a6) of hTau40^AT mice, compared to aged-matched WT mice (a1, a3, a5). Iba1 staining indicates microgliosis in 10 months old hTau40^AT mice (a8) compared to WT (a7). Note that microglia of hTau40^AT mice show an activated non-phagocytic phenotype with retracted, thicker processes (a8) compared to resting microglial cells of WT mice (a7). Activated microglia are detected by CD45 (a10) and CD11b (a12) at 5 months of age in hTau40^AT mice, whereas WT mice show no reaction (a9 and a11). Additionally, 10 months old hTau40^AT mice show IL1ß-positive pyramidal CA1-neurons (a14) and TLR2-immunoreactive glial cells (a16) in the hippocampus, compared to non-reactive WT mice (a13, a15). b Western blots of cortical extracts indicate increased levels of GFAP, Iba1, iNOS and CD11b in hTau40^AT mice compared to WT mice. ß-actin serves as loading control. c Densitometric analysis of western blots (b) for inflammatory proteins (GFAP, Iba1, iNOS and CD11b), all normalized to ß-actin. The red bars indicate an increase of neuroinflammatory processes due to hTau40^AT -expression. Statistics: two-sided t test or Mann–Whitney-U-test indicate significant differences between WT and hTau40^AT mice (*:p < 0.05; **:p < 0.01). Each bar represents mean ± SEM of n = 4 animals. WT: wildtype; A152T: hTau40^AT transgenic mouse strain; CA: cornu ammonis; mo: months; IL1ß, interleukin 1 beta, TLR2, Toll like receptor 2; iNOS, inducible nitric oxide synthase; n.s., not significant; Scale bars: 20 μm (a7-12, a15-16), 50 μm (a1-6, a13-14)