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. 2021 Dec 3;5(3):e202101183. doi: 10.26508/lsa.202101183

Figure 4. Genetic reduction in Arrb1 alleviates tauopathy in vivo.

Figure 4.

(A) Confocal images of 7-mo-old PS19 and PS19/Arrb1+/− littermates hippocampus stained for phospho-tau, pS199/pS202 (scale bar = 10 μm). White boxes are magnified below. Representative images are shown. (B) Quantification of pS199/pS202 tau intensity. n = 4/genotype. #P < 0.0001. Unpaired t test. (C) Sarkosyl-soluble and insoluble extracts from 7-mo-old PS19 and PS19/Arrb1+/− brains were immunoblotted for β-arrestin1, tau, and actin. Representative blots are shown. (D, E) Quantification of sarkosyl-soluble and insoluble tau levels. n = 5/genotype. **P < 0.005. Unpaired t test. (F) Morris water maze shows the latency of 6-mo-old PS19 and PS19/Arrb1−/− littermates during 4-d training test (WT:18 mice, PS19:16 mice, and PS19/Arrb1−/−:7 mice). **P < 0.005. Two-way ANOVA with Dunnett’s post hoc test. (G) Quantification of time spent in target quadrant (s) during 24-h probe. **P < 0.005,*P < 0.05. One-way ANOVA with Dunnett’s post hoc test. (H) Quantification of number of times entered into the target zone during 24-h probe. **P < 0.005. One-way ANOVA with Dunnett’s post hoc test. (I) Quantification of average swim speed (s). No significant difference between all genotypes. (J) Input–output analysis from 4-mo-old WT, PS19, and PS19/Arrb1+/− acute slices. (WT: 33 slices, 5 mice; PS19: 32 slices, 5 mice; PS19/Arrb1+/−: 30 slices, 4 mice). No significant differences observed. (K) Paired pulse facilitation analysis from 4-mo-old WT, PS19, and PS19/Arrb1+/− acute slices. (WT: 33 slices, 5 mice; PS19: 40 slices, 5 mice; PS19;Arrb1+/−:35 slices, 4 mice). Two-way ANOVA with Dunnett’s post hoc test. #P < 0.0001: 20–180 ms, WT versus PS19. ***P < 0.0005: 20 ms, PS19 versus PS19/Arrb1+/−. **P < 0.005: 200–260 ms, WT versus PS19. *P < 0.05: 280–300 ms, WT versus PS19; 40,100, & 120 ms, PS19 versus PS19/Arrb1+/−. (L) Long-term potentiation induced by theta burst stimulation. (WT: 31 slices, 5 mice; PS19: 29 slices, 5 mice; PS19/Arrb1+/−:31 slices, 4 mice). Two-way ANOVA with Dunnett’s post hoc test. *P< 0.0001 in all time points, WT versus PS19 and PS19/Arrb1+/− versus PS19. All data are presented as mean ± SEM.