(A) Schematic diagram showing experimental procedure: AAV-GFP/P301L-hTau was injected into MEC of 4-month-old C57BL/6 mice. Seven days later, LPS or PBS and GC were injected intraperitoneally twice a week for 5 weeks. Behavioral tests, microdialysis and biochemical assays were performed subsequently. (B) No difference in motor function between the four groups of mice was detected. (C) In the EPM test, LPS enhanced hTau-induced anxiety-like behavior, which could be partially restored by GC treatment. (D) LPS enhanced hTau-induced memory impairment shown by the further decreased NOR Index, and GC ameliorated LPS effect. (E) In MWM training, the escape latency of the P301L-LPS mice increased compared with the P301L-PBS mice at day 3 and 5. Time factor, DF = 4, F(4, 448) = 32.4, P < 0.0001; treatment factor, DF = 3, F(3, 448) = 5.225, P = 0.0015; Interaction, P > 0.05. (F) LPS enhanced hTau-induced memory impairment shown by the decreased crossing times at target quadrant after removed the platform, GC partially antagonized LPS effect. Data was present as mean ± SEM (n = 9–11 each group, one-way ANOVA followed by Bonferroni post hoc test (B,C,D,F), two-way ANOVA followed by Bonferroni post hoc test (E)). *, P < 0.05.