Fig. 1

sEH inhibition rescues neuronal and synapse loss and improves cognitive function in PS19 mice. (A) Quantification of percentage time exploring the novel object in the novel object recognition test performed in 9-9.5-month-old mice. The dashed line represents a 50% chance of random object exploration. Wild-type mice with vehicle treatment (WT_Veh): n = 10♂ and 9♀; Wild-type mice with TPPU treatment (WT_TPPU): n = 12♂ and 9♀; PS19 mice with vehicle treatment (PS19_Veh): n = 8♂and 9♀; and PS19 mice with TPPU treatment (PS19_TPPU): n = 10 ♂and 11♀. (B) Contextual (left) and cued (right) fear conditioning test performed in 9-9.5-month-old mice. WT_Veh: n = 11♂ and 9♀; WT_TPPU: n = 12 ♂and 9♀; PS19_Veh: n = 8♂ and 9♀; PS19_TPPU: n = 10♂ and 11♀. (C) Representative NeuN immunofluorescence staining images in hippocampus of WT_Veh, WT_TPPU, PS19_Veh, and PS19_TPPU mice at 9.5–10 months. Rectangles mark CA1 (red) and dentate gyrus (DG; green) areas selected for quantification. Scale bar: 200 μm. (D) Estimate of neuronal numbers in CA1 (left) and DG (right) using unbiased stereology. n = 3♂ and 3♀ per group. (E) Representative images of presynaptic marker Bassoon (red) and postsynaptic marker Homer1 (green) immunofluorescence staining in CA1 area of hippocampus from 9.5-10-month-old mice. Colocalized puncta are marked by white circles. Scale bar: 3 µm. (F) Quantification of relative number of Bassoon⁺ puncta, Homer1⁺ puncta and colocalized Bassoon⁺ and Homer1⁺ puncta (percentage of WT_Veh). n = 4♂ and 4♀ per group. Filled circle: ♂; open circle: ♀. Data are presented as mean ± SEM. One-way ANOVA with Tukey’s multiple comparison test. *p < 0.05; **p < 0.01; ***p < 0.001; ****p < 0.0001. See also Figures S2 and S3