Brain areas involved with obsessive-compulsive disorder present different DNA methylation modulation

Autor: Vanessa de Jesus Rodrigues de Paula, Ariane Cristine Moretto, Carlos Augusto Pasqualucci, Renata Elaine Paraizo Leite, Renata Eloah de Lucena Ferretti-Rebustini, Beny Lafer, Arthur Sant’Anna Feltrin, Helena Brentani, Bianca Lisboa, Mariana Maschietto, Kátia Cristina de Oliveira, Euripedes Constantino Miguel, Érika Dionisio Akiyama, Wilson Jacob-Filho, Caroline Camilo, Claudia K. Suemoto, Lea T. Grinberg, Vinicius Daguano Gastaldi, Marcelo Q. Hoexter
Rok vydání: 2021
Předmět:
Zdroj: BMC Genomic Data
ISSN: 2730-6844
Popis: Background Obsessive-compulsive disorder (OCD) is characterized by intrusive thoughts and repetitive actions, that presents the involvement of the cortico-striatal areas. The contribution of environmental risk factors to OCD development suggests that epigenetic mechanisms may contribute to its pathophysiology. DNA methylation changes and gene expression were evaluated in post-mortem brain tissues of the cortical (anterior cingulate gyrus and orbitofrontal cortex) and ventral striatum (nucleus accumbens, caudate nucleus and putamen) areas from eight OCD patients and eight matched controls. Results There were no differentially methylated CpG (cytosine-phosphate-guanine) sites (DMSs) in any brain area, nevertheless gene modules generated from CpG sites and protein-protein-interaction (PPI) showed enriched gene modules for all brain areas between OCD cases and controls. All brain areas but nucleus accumbens presented a predominantly hypomethylation pattern for the differentially methylated regions (DMRs). Although there were common transcriptional factors that targeted these DMRs, their targeted differentially expressed genes were different among all brain areas. The protein-protein interaction network based on methylation and gene expression data reported that all brain areas were enriched for G-protein signaling pathway, immune response, apoptosis and synapse biological processes but each brain area also presented enrichment of specific signaling pathways. Finally, OCD patients and controls did not present significant DNA methylation age differences. Conclusions DNA methylation changes in brain areas involved with OCD, especially those involved with genes related to synaptic plasticity and the immune system could mediate the action of genetic and environmental factors associated with OCD.
Databáze: OpenAIRE