Effects of valproic acid on transcript levels in neurotrophin signaling pathway in mice hippocampus according to the implementation period

Abstract

Abstract Background/Aim Valproic acid (VPA), is an antiepileptic drug and it has been known for a long time that exposure to VPA in the fetal period causes many behavioral, cognitive, and structural disorders. In this study, we aimed to evaluate the effects of the implementation period of VPA during pregnancy on both behavioral tests and the expression of 45 key genes belonging to the neurotrophin signaling pathway. Methods The study was designed to form four different groups of five female mice in each group. The experimental and control groups were divided into mature (n = 5) and immature (n = 5) subgroups, respectively. VPA (500 mg/kg dose) was subcutaneously administered to the experimental groups. All mice were first tested for behavioral changes, and then the hippo-campal tissues were used for RNA isolation. The expression levels of 45 transcripts associated with the neurotrophin signaling pathway were determined by real-time RT-PCR in the hippocampus. Results No differences were found between the groups in any of the behavioral tests. When gene expression was examined, there was a difference between the groups in the transcript levels of Ngf(neurotrophic growth factor), Ntrk2 (neurotrophic receptor tyrosine kinase 2), Shc1 (SHC adaptor protein 1), Chka (choline kinase alpha), and Mapk1 (mitogen-activated protein kinase 1) genes. Conclusions This study demonstrated the effects of VPA on transcript levels at different maturation stages. We believe that it is important to explain the structural and cognitive teratogenic side effects caused by VPA in human fetuses using genes whose expression changes.