Abstract
Background. Gabapentin and lamotrigine are widely used anticonvulsants prescribed to pregnant women with epilepsy. Gabapentin is a gamma-aminobutyric acid analog that reduces glutamate levels, and lamotrigine blocks sodium channels and reduces the release of glutamate and aspartate. These drugs are able to cross the placenta and potentially affect the development of the fetal brain, causing worrisome changes in fetal neurodevelopment. Undifferentiated neuronal cells were taken from the hippocampal tissue of 18-day-old rat embryos and cultured in Neurobasal medium for 20 days. Neuronal differentiation was performed in cells treated with gabapentin and lamotrigine (25 μg/mL). In order to examine gene expression, total RNA was extracted from neurons and the miRNA content of the genes was determined by real-time PCR. The t-test and ANOVA were used to compare the mean values between groups.
Methods. Undeveloped neural cells were taken from the hippocampus of 18-day-old rat embryos and cultured in Neurobasal medium for 20 days. Development of neural cells was followed in cells treated with gabapentin and lamotrigine (25μg/mL ). Additionally, to analyze gene expression, total RNA was extracted and the contents of miRNA related to genes were evaluated by real-time PCR.
Results. After 20 days, neurons in control media showed normal growth, while drug-treated groups showed abnormal dendrite and axon formation and disrupted soma morphology. Gene expression analysis revealed upregulation of MicroRNA-9 gene in both of the treatment groups compared to the control group. However, the expression level of MicroRNA-107 reduced remarkably in treated neurons.
Conclusion. Considering the changes in the morphology and gene expression and given the ability of the drugs to cross the placenta, these drugs should be prescribed with caution during pregnancy, balancing maternal needs with potential risks to the fetus.
Practical Implications. The findings of this study show that the use of anticonvulsant drugs during pregnancy affects the morphology of fetal nerve cells and prevents their growth. These drugs can also change the expression level of miRNAs that are effective in the development of the nervous system.