Alcohol consumption, depression, overweight and cortisol levels as determining factors for  NR3C1  gene methylation

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Abstract

The NR3C1 glucocorticoid receptor (GR) gene is a component of the stress response system, which can be regulated by epigenetic mechanisms. NR3C1 methylation has been associated with trauma and mental issues, including depression, post-traumatic stress, anxiety, and personality disorders. Previous studies have reported that stressful events are involved in NR3C1 gene methylation, suggesting that its regulation under environmental effects is complex. The present study aimed to analyze associations involving stressors such as socioeconomic status, health conditions, and lifestyle in relation to NR3C1 methylation in adults. This study included 386 individual users of the Brazilian Public Unified Health System (SUS), and evaluated socioeconomic and health conditions, body mass index, cortisol levels, and lifestyle. Data were correlated with NR3C1 methylation, determined using DNA pyrosequencing. The results showed that alcohol consumption, overweight, and high cortisol levels were related to NR3C1 demethylation, while depression was related to its methylation. Habits, lifestyle, and health status may influence NR3C1 gene regulation via methylation, revealing the complexity of environmental impacts on NR3C1 methylation.

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Most cited references 58

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The objective was to provide guidelines to clinicians for the evaluation, treatment, and prevention of vitamin D deficiency with an emphasis on the care of patients who are at risk for deficiency. The Task Force was composed of a Chair, six additional experts, and a methodologist. The Task Force received no corporate funding or remuneration. Consensus was guided by systematic reviews of evidence and discussions during several conference calls and e-mail communications. The draft prepared by the Task Force was reviewed successively by The Endocrine Society's Clinical Guidelines Subcommittee, Clinical Affairs Core Committee, and cosponsoring associations, and it was posted on The Endocrine Society web site for member review. At each stage of review, the Task Force received written comments and incorporated needed changes. Considering that vitamin D deficiency is very common in all age groups and that few foods contain vitamin D, the Task Force recommended supplementation at suggested daily intake and tolerable upper limit levels, depending on age and clinical circumstances. The Task Force also suggested the measurement of serum 25-hydroxyvitamin D level by a reliable assay as the initial diagnostic test in patients at risk for deficiency. Treatment with either vitamin D(2) or vitamin D(3) was recommended for deficient patients. At the present time, there is not sufficient evidence to recommend screening individuals who are not at risk for deficiency or to prescribe vitamin D to attain the noncalcemic benefit for cardiovascular protection.

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Ian Weaver, Nadia Cervoni, Frances Champagne … (2004)

Here we report that increased pup licking and grooming (LG) and arched-back nursing (ABN) by rat mothers altered the offspring epigenome at a glucocorticoid receptor (GR) gene promoter in the hippocampus. Offspring of mothers that showed high levels of LG and ABN were found to have differences in DNA methylation, as compared to offspring of 'low-LG-ABN' mothers. These differences emerged over the first week of life, were reversed with cross-fostering, persisted into adulthood and were associated with altered histone acetylation and transcription factor (NGFI-A) binding to the GR promoter. Central infusion of a histone deacetylase inhibitor removed the group differences in histone acetylation, DNA methylation, NGFI-A binding, GR expression and hypothalamic-pituitary-adrenal (HPA) responses to stress, suggesting a causal relation among epigenomic state, GR expression and the maternal effect on stress responses in the offspring. Thus we show that an epigenomic state of a gene can be established through behavioral programming, and it is potentially reversible.

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DNA methylation and its basic function.

Lisa Moore, Thuc Le, Guoping Fan (2013)

In the mammalian genome, DNA methylation is an epigenetic mechanism involving the transfer of a methyl group onto the C5 position of the cytosine to form 5-methylcytosine. DNA methylation regulates gene expression by recruiting proteins involved in gene repression or by inhibiting the binding of transcription factor(s) to DNA. During development, the pattern of DNA methylation in the genome changes as a result of a dynamic process involving both de novo DNA methylation and demethylation. As a consequence, differentiated cells develop a stable and unique DNA methylation pattern that regulates tissue-specific gene transcription. In this chapter, we will review the process of DNA methylation and demethylation in the nervous system. We will describe the DNA (de)methylation machinery and its association with other epigenetic mechanisms such as histone modifications and noncoding RNAs. Intriguingly, postmitotic neurons still express DNA methyltransferases and components involved in DNA demethylation. Moreover, neuronal activity can modulate their pattern of DNA methylation in response to physiological and environmental stimuli. The precise regulation of DNA methylation is essential for normal cognitive function. Indeed, when DNA methylation is altered as a result of developmental mutations or environmental risk factors, such as drug exposure and neural injury, mental impairment is a common side effect. The investigation into DNA methylation continues to show a rich and complex picture about epigenetic gene regulation in the central nervous system and provides possible therapeutic targets for the treatment of neuropsychiatric disorders.

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Author and article information

Contributors

Adriana Madeira Alvares-da-Silva: adriana.biomol@gmail.com

Journal

Journal ID (nlm-ta): Sci Rep

Journal ID (iso-abbrev): Sci Rep

Title: Scientific Reports

Publisher: Nature Publishing Group UK (London )

ISSN (Electronic): 2045-2322

Publication date (Electronic): 24 March 2021

Publication date PMC-release: 24 March 2021

Publication date Collection: 2021

Volume: 11

Electronic Location Identifier: 6768

Affiliations

[1 ]GRID grid.412371.2, ISNI 0000 0001 2167 4168, Biotechnology/Renorbio Graduate Program, , Universidade Federal do Espirito Santo, ; Vitoria, ES Brazil

[2 ]GRID grid.412371.2, ISNI 0000 0001 2167 4168, Department of Pharmacy and Nutrition, , Universidade Federal do Espirito Santo, ; Alegre, ES Brazil

[3 ]GRID grid.412371.2, ISNI 0000 0001 2167 4168, Graduate Program in Forest Sciences, , Universidade Federal do Espirito Santo, ; Alegre, ES Brazil

[4 ]GRID grid.412371.2, ISNI 0000 0001 2167 4168, Department of Agronomia, , Universidade Federal do Espirito Santo, ; Alegre, ES Brazil

[5 ]Fluminense Federal Institute, Campos dos Goytacazes, RJ Brazil

[6 ]GRID grid.427783.d, ISNI 0000 0004 0615 7498, Molecular Oncology Research Center, , Hospital do Câncer de Barretos, ; Barretos, SP Brazil

[7 ]GRID grid.413320.7, ISNI 0000 0004 0437 1183, A. C. Camargo Cancer Center, ; São Paulo, SP Brazil

[8 ]GRID grid.412371.2, ISNI 0000 0001 2167 4168, Department of Medicina Veterinária, , Universidade Federal do Espirito Santo, ; Alegre, ES Brazil

[9 ]GRID grid.412371.2, ISNI 0000 0001 2167 4168, Department of Social and Developmental Psychology, , Universidade Federal do Espírito Santo, ; Vitoria, ES Brazil

[10 ]GRID grid.412371.2, ISNI 0000 0001 2167 4168, Department of Morphology, Health Science Center, , Universidade Federal do Espirito Santo, ; Vitoria, ES Brazil

[11 ]GRID grid.412371.2, ISNI 0000 0001 2167 4168, Departamento de Biologia, , Universidade Federal do Espirito Santo, Alto Universitário Sem Número, ; Alegre, ES 29500000 Brazil

Article

Publisher ID: 86189

DOI: 10.1038/s41598-021-86189-z

PMC ID: 7990967

PubMed ID: 33762648

SO-VID: 120241a7-bae6-46af-8f0b-fa2e58680dac

License:

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

History

Date received : 1 June 2020

Date accepted : 9 March 2021

Funding

Funded by: Higher Education Personnel Improvement Coordination - Brazil (CAPES)

Funded by: FAPES (Fundação de Apoio a Pesquisa do Esperíto Santo) through SUS Research Project (PPSUS)

Funded by: Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Award ID: 424130/2018-1

Award Recipient : Adriana Madeira Alvares-da-Silva

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ScienceOpen disciplines: Uncategorized

Keywords: epigenetics and behaviour,dna methylation

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ScienceOpen disciplines: Uncategorized

Keywords: epigenetics and behaviour, dna methylation

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Alcohol consumption, depression, overweight and cortisol levels as determining factors for NR3C1 gene methylation

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Measurement of Glucocorticoid Receptor Signaling in Major Depression

Most cited references 58

Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline.

Epigenetic programming by maternal behavior.

DNA methylation and its basic function.

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Cited by 8

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