Anticonvulsants and Chromatin-Genes Expression: A Systems Biology Investigation

Overview

Journal Front Neurosci

Date 2020 Dec 17

PMID 33328862

Authors

Thayne Woycinck Kowalski

Julia do Amaral Gomes

Marilea Furtado Feira

Agata de Vargas Dupont

Mariana Recamonde-Mendoza

Fernanda Sales Luiz Vianna

Affiliations

Soon will be listed here.

Abstract

Embryofetal development is a critical process that needs a strict epigenetic control, however, perturbations in this balance might lead to the occurrence of congenital anomalies. It is known that anticonvulsants potentially affect epigenetics-related genes, however, it is not comprehended whether this unbalance could explain the anticonvulsants-induced fetal syndromes. In the present study, we aimed to evaluate the expression of epigenetics-related genes in valproic acid, carbamazepine, or phenytoin exposure. We selected these three anticonvulsants exposure assays, which used murine or human embryonic stem-cells and were publicly available in genomic databases. We performed a differential gene expression (DGE) and weighted gene co-expression network analysis (WGCNA), focusing on epigenetics-related genes. Few epigenetics genes were differentially expressed in the anticonvulsants' exposure, however, the WGCNA strategy demonstrated a high enrichment of chromatin remodeling genes for the three drugs. We also identified an association of 46 genes related to Fetal Valproate Syndrome, containing and , and nine genes to Fetal Hydantoin Syndrome, including , and . The evaluation of stem-cells under drug exposure can bring many insights to understand the drug-induced damage to the embryofetal development. The candidate genes here presented are potential biomarkers that could help in future strategies for the prevention of congenital anomalies.

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