Fig. 6: Normalization of adult behavioral and cognitive deficits in HERV-W ENV mice through pharmacological inhibition of LSD1.

Male transgenic CAG^HERV-Wenv mice (TG) and wild-type (WT) littermates were treated with the LSD1 inhibitor, ORY-1001, or corresponding vehicle (VEH). A The line plot depicts the means ± s.e.m. of time spent with the unfamiliar mouse or dummy object, whereas the scatter plot (with overlaid means ± s.e.m.) shows the social preference index (values > 0 represent a preference toward the unfamiliar mouse) in phase 1 of the social interaction test. ^§p < 0.001, reflecting the significant main effect of object (F_(1,76) = 87.53) in repeated-measures ANOVA. B The line plot depicts the means ± s.e.m. of time spent with the novel or familiar mouse, whereas the scatter plot (with overlaid means ± s.e.m.) depicts the social memory index (values > 0 represent a preference toward the novel mouse) in phase 2 of the social interaction test. ^#p < 0.001 and ⁺p < 0.001, reflecting the significant difference between novel and familiar mouse exploration in VEH-treated WT mice and in ORY-1001-treated WT or TG mice, respectively, based on Šidák post-hoc test after the presence of a significant 3-way interaction between genotype, object and treatment (F_(1,76) = 23.68, p < 0.001) in repeated-measures ANOVA. *p < 0.05 and **p < 0.01, based on Tukey’s post-hoc test following a significant 2-way interaction between genotype and treatment (F_(1,76) = 7.61, p < 0.01) in ANOVA. C Number of buried marbles and distance moved during the marble burying test. **p < 0.01, based on Tukey’s post-hoc test following a significant 2-way interaction between genotype and treatment (F_(1,76) = 5.21, p < 0.05) in ANOVA. D The line plot depicts the means ± s.e.m. of time spent with the novel or familiar object, whereas the scatter plot (with overlaid means ± s.e.m.) depicts the novel object recognition memory index (values > 0 represent a preference toward the novel object) in the novel object recognition test. ^#p < 0.001 and ⁺p < 0.01, reflecting the significant difference between novel and familiar object exploration in VEH-treated WT mice and in ORY-treated WT or TG mice, respectively, based on Šidák multiple comparison post-hoc test after the presence of a significant 3-way interaction between genotype, object and treatment (F_(1,76) = 19.24, p < 0.001) in repeated-measures ANOVA; *p < 0.05 and ***p < 0.001, based on Tukey’s post-hoc test following a significant 2-way interaction between genotype and treatment (F_(1,76) = 4.32, p < 0.05) in ANOVA. E The line plots depict the means ± s.e.m. of % PPI averaged across different pulse intensities (100, 110 and 120 dB_A); the scatter plot (with overlaid means ± s.e.m.) depicts the mean % PPI across all prepulse and pulse intensities. ***p < 0.001, based on Tukey’s post-hoc test following a significant 2-way interaction between genotype and treatment (F_(1,76) = 17.05, p < 0.001) in repeated-measures ANOVA. F The line plots depict the means ± s.e.m. of startle reactivity (in arbitrary units, AU) to 100-, 110- and 120-dB_A pulse stimuli, whereas the scatter plot (with overlaid means ± s.e.m.) shows the mean startle reactivity (in AU) across all pulse intensities. n(WT/VEH) = 20 mice, n(TG/VEH) = 20 mice, n(WT/ORY-1001) = 19 mice, and n(TG/ORY-1001) = 21 mice.