The Ability of Risperidone To Methylate The ST8sia2 and ST8sia4 Genes and Its Effect on Sialic Acid Levels in The Brains of Embryos and Offspring of Albino Rats

Abstract

Background

Epigenetic modifications, particularly DNA methylation, play an important role in regulating gene expression during brain development. The ST8sia2 and ST8sia4 genes are involved in the biosynthesis of polysialic acid, a molecule that contributes to neuronal development and plasticity. Aim of the Study: The present study aimed to investigate the effects of maternal exposure to sulforaphane and risperidone during pregnancy and the early postnatal period on the DNA methylation patterns of the ST8sia2 and ST8sia4 genes and sialic acid levels in the brains of rat fetuses and offspring at different developmental stages. Methodology: Eighteen healthy adult female albino rats, aged 11–12 weeks were randomly allocated into three experimental groups: saline control, sulforaphane (SFN), and risperidone (RIS). Results: The methylation patterns of both ST8sia2 and ST8sia4 differed among the experimental groups and developmental stages. For ST8sia2, methylation was detected in 13 of 86 samples (15.1%), including 12 samples from the RIS group and one from the control group, whereas no methylation was detected in the SFN group. The differences among groups were not statistically significant at E14 (P = 0.085), but became significant at P0 (P = 0.028) and P7 (P = 0.023), with a highly significant difference when all developmental stages were considered together (P < 0.001). For ST8sia4, methylation was detected in 9 of 86 samples (10.5%), all of which belonged to the RIS group. No methylation was detected in either the control or SFN groups. The differences were not significant at E14 (P = 0.307) or P0 (P = 0.090), but a significant difference was observed at P7 (P = 0.023). Sialic acid concentrations also varied among the groups. At E14, no significant differences were observed. At P0 and P7, however, sialic acid levels were significantly lower in the RIS group than in both the saline and SFN groups, whereas no significant difference was observed between the saline and SFN groups. Conclusion: Maternal exposure to risperidone was associated with alterations in the DNA methylation patterns of the ST8sia2 and ST8sia4 genes in the brains of rat offspring, particularly during the early postnatal period. In contrast, the SFN group maintained an unmethylated pattern for both genes across the examined developmental stages. Risperidone exposure was also associated with reduced brain sialic acid levels at P0 and P7.