Fig. 4. 7,8-DHF treatment rescued autistic-like behaviors in ELS-exposed D2+/− mice. (A) Experimental design for treatment with 7,8-DHF, behavioral tests, and time points for sacrifice. 7,8-DHF was intraperitoneally injected at the dose of 10 mg/kg/day for 3 days, and behavioral tests were carried out on day 4. (B, C) Representative heatmaps showing exploratory activity in the three-chamber test of normally raised WT mice and ELS-exposed D2+/− mice treated with 7,8-DHF or vehicle (B). The amounts of time spent in each chamber for the mouse groups are presented in (C). n= 5–7 animals (WT, CON+Veh: p<0.0001; WT, CON+DHF: p= 0.0042; D2+/−, ELS+Veh: p=0.5986, D2+/−; ELS+DHF: p=0.0002). (D, E) The social interaction time spent sniffing in the home-cage social interaction test (D) and grooming time (E) of normally raised WT mice and ELS-exposed D2+/− mice treated with 7,8-DHF or vehicle. n=5~7 animals (Home-cage social interaction: genotype effect, F(1, 19)=9.227, p=0.0068; DHF effect, F(1, 19)=0.5098, p=0.4839; genotype x DHF interaction, F(1,19)=2.703, p=0.1166; Grooming: genotype effect, F(1, 21)=10.04, p=0.0046; DHF effect, F(1, 21)=25.07, p<0.0001; genotype x DHF interaction, F(1, 21)=11.75, p=0.0025). (F) Real-time PCR data showing transcript levels of TrkB, tBdnf, and Bdnf4 in the dorsal striatum of normally raised WT mice and ELS-exposed D2+/− mice treated with 7,8-DHF or vehicle (F). n=3~4 animals, 3~5 PCR repeats (TrkB: genotype effect, F(1, 14)=5.693, p=0.0317; DHF effect, F(1, 14)=11.95, p=0.0039; genotype x DHF interaction, F(1, 14)=11.46, p=0.0044). (G~J) Western blots showing TrkB, BDNF (G), p-AKT, AKT, p-ERK1/2, ERK1/2, p-CREB, CREB and β-Actin (I) levels in the dorsal striatum of normally raised WT mice and ELS-exposed D2+/− mice treated with 7,8-DHF or vehicle. Quantification of Western blots (H, J). n=3~4 animals, 3~5 repeats (TrkB: genotype effect, F(1, 12)=9.596, p=0.0092; DHF effect, F(1, 12)=9.814, p=0.0086; genotype x DHF interaction, F(1, 12)=0.2431, p=0.6309; BDNF: genotype effect, F(1, 8)=1.936, p=0.2015; DHF effect, F(1, 8)=3.507, p=0.0980; genotype x DHF interaction, F(1, 8)=0.2157, p=0.6547). Data are presented as mean±SEM. * and ** denote differences between the indicated groups at p<0.05 and p<0.01, respectively (Student's t-test or two-way ANOVA followed by Holm-Sidak post hoc test).
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