Anticonvulsants and Chromatin-Genes Expression: A Systems Biology Investigation

Frontiers in Neuroscience

Thayne Woycinck Kowalski¹  Ágata de Vargas Dupont³  Mariléa Furtado Feira³  Mariana Recamonde-Mendoza⁴  Julia do Amaral Gomes⁷  Fernanda Sales Luiz Vianna⁷ 

[1] Bioinformatics Core, Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, Brazil;Centro Universitário CESUCA, Cachoeirinha, Brazil;Genomic Medicine Laboratory, Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, Brazil;Institute of Informatics, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil;Laboratory of Immunobiology and Immunogenetics, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil;National Institute of Population Medical Genetics (INAGEMP), Porto Alegre, Brazil;National System of Information on Teratogenic Agents (SIAT), Medical Genetics Service, Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, Brazil;Postgraduation Program in Genetics and Molecular Biology, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil;

关键词: WGCNA;    epigenetics;    antiepileptics;    teratogen;    valproic acid;    phenytoin;   

DOI  :  10.3389/fnins.2020.591196

来源: DOAJ

【 摘 要 】

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 SMARCA2 and SMARCA4, and nine genes to Fetal Hydantoin Syndrome, including PAX6, NEUROD1, and TSHZ1. 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.

【 授权许可】

Unknown