DNA methylation in regulatory elements of the FKBP5 and NR3C1 gene in mother-child binomials with depression.

Autor: Mendonça MS; Laboratory of Biotechnology, Universidade Estadual do Norte Fluminense Darcy Ribeiro, Campos dos Goytacazes, Rio de Janeiro 28013-602, Brazil., Mangiavacchi PM; Laboratory of Reproduction and Animal Breeding, Universidade Estadual do Norte Fluminense Darcy Ribeiro, Campos dos Goytacazes, Rio de Janeiro 28013-602, Brazil., Mendes AV; Department of Neurosciences and Behavioral Sciences, USP, Ribeirão Preto, São Paulo 14051-140, Brazil., Loureiro SR; Department of Neurosciences and Behavioral Sciences, USP, Ribeirão Preto, São Paulo 14051-140, Brazil., Martín-Santos R; Instituto Nacional de Ciência e Tecnologia Translacional em Medicina Translational Medicine (INCT-TM), National Council for Scientific and Technological Development, São Paulo, Brazil; Department of Psychiatry and Psychology, Hospital Clínic, Institut d' Investigacions Biomedicas August Pi I Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red en Salud Mental (CIBERSAM), Instituto de Neurociencias, University of Barcelona, Barcelona 08036, Spain., Glória LS; Laboratory of Animal Science, Universidade Estadual do Norte Fluminense Darcy Ribeiro, Campos dos Goytacazes, Rio de Janeiro 28013-602, Brazil., Marques W; Department of Neurosciences and Behavioral Sciences, USP, Ribeirão Preto, São Paulo 14051-140, Brazil., De Marco SPG; Department of Neurosciences and Behavioral Sciences, USP, Ribeirão Preto, São Paulo 14051-140, Brazil., Kanashiro MM; Laboratory of Recognition Biology, North Fluminense State University (UENF), Campos dos Goytacazes, Rio de Janeiro 28013-602, Brazil., Hallak JEC; Department of Neurosciences and Behavioral Sciences, USP, Ribeirão Preto, São Paulo 14051-140, Brazil; Instituto Nacional de Ciência e Tecnologia Translacional em Medicina Translational Medicine (INCT-TM), National Council for Scientific and Technological Development, São Paulo, Brazil., Crippa JAS; Department of Neurosciences and Behavioral Sciences, USP, Ribeirão Preto, São Paulo 14051-140, Brazil; Instituto Nacional de Ciência e Tecnologia Translacional em Medicina Translational Medicine (INCT-TM), National Council for Scientific and Technological Development, São Paulo, Brazil., Rios ÁFL; Laboratory of Biotechnology, Universidade Estadual do Norte Fluminense Darcy Ribeiro, Campos dos Goytacazes, Rio de Janeiro 28013-602, Brazil. Electronic address: aflrios@uenf.br.
Jazyk: angličtina
Zdroj: Journal of affective disorders [J Affect Disord] 2023 Jun 15; Vol. 331, pp. 287-299. Date of Electronic Publication: 2023 Mar 16.
DOI: 10.1016/j.jad.2023.03.031
Abstrakt: Background: The FKBP5 and NR3C1 genes play an important role in stress response, thus impacting mental health. Stress factor exposure in early life, such as maternal depression, may contribute to epigenetic modifications in stress response genes, increasing the susceptibility to different psychopathologies. The present study aimed to evaluate the DNA methylation profile in maternal-infant depression in regulatory regions of the FKBP5 gene and the alternative promoter of the NR3C1 gene.
Methods: We evaluated 60 mother-infant pairs. The levels of DNA methylation were analyzed by the MSRED-qPCR technique.
Results: We observed an increased DNA methylation profile in the NR3C1 gene promoter in children with depression and children exposed to maternal depression (p < 0.05). In addition, we observed a correlation of DNA methylation between mothers and offspring exposed to maternal depression. This correlation shows a possible intergenerational effect of maternal MDD exposure on the offspring. For FKBP5, we found a decrease in DNA methylation at intron 7 in children exposed to maternal MDD during pregnancy and a correlation of DNA methylation between mothers and children exposed to maternal MDD (p < 0.05).
Limitations: Although the individuals of this study are a rare group, the sample size of the study was small, and we evaluated the DNA methylation of only one CpG site for each region.
Conclusion: These results indicate changes in DNA methylation levels in regulatory regions of FKBP5 and NR3C1 in the mother-child MDD context and represent a potential target of studies to understand the depression etiology and how it occurs between generations.
Competing Interests: Declaration of competing interest JAC and JECH are co-inventors (Mechoulam R, Crippa JA, Guimaraes FS, Zuardi A, Hallak, JE, and Breuer A) of the patent “Fluorinated CBD compounds, compositions and uses thereof. Pub. No.: WO/2014/108899. International Application No.: PCT/IL2014/050023” Def. US no. Reg. 62193296; July 29, 2015; INPI on August 19, 2015 (BR1120150164927). The University of São Paulo has licensed the patent to Phytecs Pharm (USP Resolution 15.1.130002.1.1). USP has an agreement with Prati-Donaduzzi (Toledo, Brazil) to “develop a pharmaceutical product containing synthetic CBD and prove its safety and therapeutic efficacy in the treatment of epilepsy, schizophrenia, Parkinson's disease, and anxiety disorders.” JAC has received travel support from and is a medical advisor of the SCBD Centre, and has a grant from the University Global Partnership Network (UGPN) – “Global priorities in cannabinoid research excellence.” JAC is member of the international advisory board of the Australian Centre for Cannabinoid Clinical and Research Excellence (ACRE; funded by the National Health and Medical Research Council through the Centre of Research Excellence). The other authors report no conflicts of interest.
(Copyright © 2023 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: