Fig. 1

LPS-induced tau phosphorylation and microglial activation are exacerbated in Cx₃cl1^105Δ mice. a–d Two-month-old fractalkine (Cx₃cl1^−/−)-deficient mice and the mice exclusively expressing the chemokine domain (lacking the mucin-like domain, red) (CX₃CL1^105Δ) with a Myc tag were injected with LPS (3 mg/kg b.w; i.p) or vehicle (VEH, Hank’s balanced salt solution or HBSS) and sacrificed 24 h post-injection. e–f Western blotting of the hippocampi revealed significantly increased total tau (Tau5) (> 1.5-fold) in VEH-treated Cx₃cl1^105Δ vs. Cx₃cl1^−/− mice (mean + SEM; **p < 0.01; n = 3; two-way ANOVA followed by Tukey’s post hoc test). Both AT8/Tau5 and AT180/Tau5 ratios were significantly higher in LPS-treated Cx₃cl1^105Δ compared to LPS-treated Cx₃cl1^−/− or Non-Tg mice (mean + SEM; *p < 0.05; **p < 0.01; n = 3; two-way ANOVA with Tukey’s post hoc test). g Immunohistochemistry (IHC) analysis revealing a modest increase in AT8 (pS199/pS202 tau) among experimental genotypes or between VEH- or LPS-injected mice in the CA3 hippocampal areas. Scale bar, 20 μm. h–k IHC showing elevated Iba1⁺/F4/80⁺ reactive microglia in VEH-treated Cx₃cl1^105Δ mice that is enhanced with LPS treatment. Quantification reveals statistically higher form factor units (higher number means more towards circular contour) for Iba1⁺ microglia in Non-Tg and Cx₃cl1^105Δ mice in LPS-treated groups (mean + SEM; ***p < 0.0001 vs. **p < 0.01 for Non-Tg with LPS; two-way ANOVA with Tukey’s post hoc test; n = 3–6 mice per group). Scale bars (h, j) 25 μm