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

Autor(es):Mostrar menos -

de Oliveira, Katia Cristina ^{[1, 2, 3]} ; Camilo, Caroline ^[3] ; Gastaldi, Vinicius Daguano ^[3] ; Feltrin, Arthur Sant'Anna ^[2] ; Garcia Lisboa, Bianca Cristina ^[3] ; Rodrigues de Paula, Vanessa de Jesus ^[3] ; Moretto, Ariane Cristine ^[1] ; Lafer, Beny ^[3] ; Hoexter, Marcelo Queiroz ^{[3, 4]} ; Miguel, Euripedes Constantino ^{[3, 4]} ; Maschietto, Mariana ^[5] ; Brentani, Helena ^{[3, 4]} ; Grp, Biobank Aging Studies

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Fac Med FMUSP, Sao Paulo - Brazil

^[2] Fed Univ ABC, Ctr Math Computat & Cognit, Sao Bernardo Do Campo - Brazil

^[3] Univ Sao Paulo, Fac Med FMUSP, Dept & Inst Psiquiatria, Rua Dr Ovidio Pires de Campos 785, LIM23 Terreo, BR-05403010 Sao Paulo - Brazil

^[4] Univ Sao Paulo, Fac Med FMUSP, Lab Psicopatol & Terapeut Psiquiatr LIM23, Sao Paulo - Brazil

^[5] Ctr Infantil Boldrini, Ctr Pesquisa, Campinas, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: BMC GENOMIC DATA; v. 22, n. 1 OCT 30 2021.
• Citações Web of Science: 0

Resumo

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. (AU)

• Processo FAPESP: 14/00591-1 - Estudos de redes de co-expressão gênica do córtex orbitofrontal e estriado (estudo post-mortem) de indivíduos portadores de TOC e controles
• Beneficiário: Bianca Cristina Garcia Lisboa
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 14/15879-0 - Estudo de biomarcadores periféricos em pacientes com transtorno obsessivo-compulsivo e controles
• Beneficiário: Kátia Cristina de Oliveira
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 13/05953-6 - Investigação de circuitos neuronais e marcadores biológicos envolvidos no transtorno obsessivo-compulsivos por meio de paradigmas comportamentais de medo e ansiedade
• Beneficiário: Ariane Cristine Moretto
• Modalidade de apoio: Bolsas no Brasil - Programa Capacitação - Treinamento Técnico
• Processo FAPESP: 11/21357-9 - Investigação de circuitos neuronais e marcadores biológicos envolvidos no transtorno obsessivo-compulsivo por meio de paradigmas comportamentais de medo e ansiedade
• Beneficiário: Eurípedes Constantino Miguel Filho
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 15/06281-7 - Investigação da regulação epigenética em tumores sólidos pediátricos
• Beneficiário: Mariana Camargo Maschietto
• Modalidade de apoio: Bolsas no Brasil - Jovens Pesquisadores