DNA methylation participated in the transgenerational transmission. (a) DNMT 1 mRNA levels were up-regulated in the hippocampus of FS rats and their F1offspring. DNMT 1 mRNA level did not change in F2 rats, the F0 generation of FS rats treated with zebularine, and FS rat offspring treated with zebularine. Zebualrine treatment did not change DNMT 1 mRNA levels in control rats. DNMT 3A and 3B mRNA levels did not differ among these groups (n = 6 for each group). (b) DNMT 1 protein expression was up-regulated in the hippocampus of FS rats and their future offspring but not in the F2 generation. Zebualrine treatment inhibited the up-regulation of DNMT 1 protein levels in F0 FS rats and the F1 offspring of FS rats but not in control and F2 rats (n = 6 for each group). DNMT 3A and 3B protein levels did not differ among them (n = 6 for each group, P > 0.05). (c) MES-induced seizure scores in adult FS rats treated with DNMT inhibitors (zebularine or 5-AZA) or saline immediately after FSs and once daily for the following 5 days in infant (n = 8 for each group). (d) MES-induced seizure scores in offspring of FS rats treated with DNMT inhibitors or saline in infant (n = 6 for each group). (e) MES-induced seizure scores in FS rats treated with DNMT inhibitors or saline in adult. C, control group; FS, 10 FS group; F1, F1 generation of FS group; F2, F2 generation of FS group; Con + Veh: control group treated with vehicle; FS + Veh: FS group treated with vehicle; (FS + Veh)-F1:offspring of FS group treated with vehicle; Error bars indicate SEM. *P < 0.05.