Fig. 5

Taprenepag improved ASD-related behavioral abnormalities and damage to TPH-2⁺ neurons in offspring exposed to VPA. (A) Schematic diagram of the implementation of the experimental plan. VPA-exposed pregnant mice received VPA at E12.5 and Tap treatment (0.5 mg/kg or 2.5 mg/kg) at E13.5. The fetal and placental experiments were carried out at E14.5. USV was conducted at P3-P11, regardless of gender. Behavioral evaluation for male mice began at P45 and was conducted under the following order: (open field, self-grooming behavior, marble burying and three-chamber social interaction assay). (B) The percentage of pregnant mice with any (at least one) fetal resorption event (%). (Control and VPA + Tap, n = 14 dams; VPA, n = 13 dams; VPA + RU486, n = 9 dams.) (C) The percentage of resorbed fetuses relative to total fetuses. (Control and VPA + Tap, n = 14 dams; VPA, n = 13 dams; VPA + RU486, n = 9 dams.) (D) The total calls for pups in 3 min in the isolation-induced distress vocalization assay. (n = 12 dams, respectively). (E) The cumulative time spent in self-grooming in 10 min. (n = 12 dams, respectively). (F) The number of marbles buried in 15 min. (n = 12 dams, respectively). (G) For sociability testing, the time of tested mice spent in the Mouse chamber and Object chamber. (n = 12 dams, respectively). (H) For the social novelty testing, time of tested mice spent in the Familiar chamber and Unfamiliar chamber. (n = 12, respectively). (I) Immunofluorescence staining of TPH-2⁺ neurons and 5-HT in the RN at P55. (J) Schematic diagram of TPH-2⁺ neurons and 5-HT and the positions of sections. (K) and (L) The mean fluorescence intensity of immunofluorescence staining TPH-2⁺ and 5-HT in RN. (n = 5 dams, respectively). Statistics were calculated by two-tailed χ2 test for (B), one-way ANOVA with Dunnett’s post hoc test for (C), (E), (F), (K) and (L) and two-way ANOVA with Tukey’s post hoc test for (D), (G) and (H). Statistical significance was denoted by *P < 0.05; **P < 0.01; ***P < 0.001; ****P < 0.0001. The graphs show the mean ± SEM