Effects of Pre-pregnancy Chronic Valproate Administration in Female Rats on Avoidance Memory and Hippocampal Gene Expression of Offspring

Abstract

Background and purpose: Valproic acid derivatives are histone deacetylases (HDACs) inhibitors. HDACs are important in epigenetic processes. Some epigenetic modifications are inherited. This study aimed at investigating the intergenerational effects of pre-pregnancy chronic valproate consumption on offspring. Materials and methods: In this experimental study, twelve female Wistar rats were randomly divided into two groups of control and valproate. For 30 days, the control group received saline and the valproate group received sodium valproate (300 mg/kg) intraperitoneally (i.p.). After mating, pregnancy, and nursing, two males and two females pup were randomly selected from the mothers and placed in the following groups: 1) male offspring of the control group, 2) female offspring of the control group, 3) male offspring of the valproate group, and 4) female offspring of the valproate group. Future experiments were followed using these groups. Avoidance memory was assessed using the shuttle box. Offspring's hippocampus were extracted and used for MECP2, HDAC2, BDNF genes expression study by qRT-PCR. Results: No significant differences were detected in avoidance memory between male and female offspring of the mothers in valproate group and that of the controls (P>0.05). There were no significant differences in MECP2, HDAC2, and BDNF genes expression between male offspring of the mothers in control and valproate groups (P>0.05). But, expression levels of these genes significantly decreased in female offspring of valproate mothers compared with those of the female offspring of the controls (P<0.05). Conclusion: Pre-pregnancy chronic valproate consumption did not affect avoidance memory in offspring. But, it seems to affect hippocampus gene expression sex-dependently.

Keywords

• avoidance memory
• bdnf
• hdac2
• mecp2
• valproate