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Fig. 2 | Alzheimer's Research & Therapy

Fig. 2

From: Selective suppression of the α isoform of p38 MAPK rescues late-stage tau pathology

Fig. 2

Oral administration of MW181 reduces hyperphosphorylated and aggregated tau in 20-month-old hTau transgenic mice. a Treatment schema for intervention for MW181 (1 mg/kg b.w.), SB239063 (5 mg/kg b.w.), or vehicle (saline) administration via oral gavage once daily for a total of 14 days. After the end date (age 20.5 months), mice were sacrificed for biochemical and neuropathological analysis. b Western blots of detergent soluble hippocampal lysates from 20.5-month-old hTau mice treated with MW181 and SB239063 show significant reduction of AT180 in MW181-treated mice compared with the vehicle-treated group. c Quantifications of AT180/Tau5 ratio show statistically significant (n = 4 for SB239063, n = 6 for MW181, and n = 6 for vehicle; mean ± SEM of IDV ratios; **p < 0.01; one-way ANOVA with Tukey’s multiple comparison test) reduction in the AT180/Tau5 ratio in the MW181-treated compared with vehicle-treated hTau mice. d Outline of the sagittal brain section identifying the hippocampal region used for quantitative morphometry for AT180. Immunohistochemistry revealed reduced AT180 specifically in the CA3/dentate gyrus of hippocampus of SB239063-treated and MW181-treated hTau mice compared with vehicle-treated controls. Scale bar: 50 μm (top panels) and 20 μm (bottom panels). e Quantitative morphometry for AT180 for groups in d (n = 3 mice per genotype; two random fields in three sections per brain were quantified; percentage mean ± SEM of AT180 immunoreactive area in the CA3 region of hippocampus; normalized to vehicle-treated group, which was 100%; *p < 0.05; one-way ANOVA with Tukey multiple comparison test). f, g Reduced levels of Sarkosyl-insoluble and AT8+ tau in the hippocampi of MW181-treated but not with SB239063-treated 20-month-old hTau mice compared with age-matched, vehicle-treated controls. g Quantifications of Sarkosyl-insoluble/Sarkosyl-soluble ratios for AT8 (left graphs) and Tau5 (right graphs) show statistically significant (n = 5 for Veh, n = 7 for MW181, and n = 3 for SB239063; mean ± SEM of IDV; **p < 0.01, ***p < 0.001, **** p <0.0001; unpaired t test) reduction in Tau5 in the Sarkosyl-insoluble fraction of MW181-treated and SB239063-treated hTau mice. h Twenty-month-old hTau mice treated with vehicle exhibited significantly reduced (*p < 0.05; one-way ANOVA with Tukey multiple comparison test; n = 5 for vehicle, n = 4 for SB239063, and n = 6 for MW181) percentage of spontaneous alternation compared with MW181-treated hTau mice in the Y-maze test. No differences in the total number of arms entered were noted. Veh vehicle

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