Epigenetic impact of chronic stress: BDNF exon IV gene methylation in high-risk professionals

IF 3.7 2区 医学 Q1 PSYCHIATRY
Bárbara Risse Quaioto , Marcele Lorentz Mattos de Souza , Aline Ribeiro Borçoi , Suzanny Oliveira Mendes , Luiz Cláudio Barreto Silva Neto , Carlos Henrique Pagani Corrêa , Ivana Alece Arantes Moreno , Amanda Sgrancio Olinda , Ester Ribeiro Cunha , Pierre Augusto Victor da Silva , Isabela de Sousa Bianchini Marins , Anita Vargas de Castro , Elisa Soares Fassarella , Bruna Pereira Sorroche , Lídia Maria Rebolho Batista Arantes , Sônia Alves Gouvea , Pedro Luiz Ferro , Elizeu Batista Borloti , Adriana Madeira Alvares-da-Silva
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引用次数: 0

Abstract

Stress is characterized by homeostatic imbalances caused by factors known as stressors. When faced with a stressor, the body activates the autonomic nervous system, the immune system, and the hypothalamic–pituitary–adrenal axis to restore homeostasis. Repeated exposure to stressful conditions can lead to epigenetic changes. Work-related stressors in high-pressure professions, can influence the epigenetics of key genes involved in brain function, including BDNF. This study investigated the relationship between BDNF DNA methylation and stress in military police officers. A total of 123 military police officers from Metropolitan Region of Grande Vitória, ES, Brazil were recruited to assess whether stress influences methylation by pyrosequencing the BDNF exon IV promoter region. A Generalized Linear Model was used to analyze the effect of stress on methylation levels, controlling for important confounding factors. The results showed that stress was significantly associated with BDNF DNA methylation at CpG 5, CpG 6, and CpG 11 in BDNF exon IV, a region that includes the binding site for the transcription factor CREB. These results indicate that the chance of occurrence of higher levels of methylation was 0.259 times higher at CpG 5, 0.471 times higher at CpG 6, and 0.461 times higher at CpG 11 in military police officers under stress than in those who did not experience stress. Based on these findings, we suggest that stress may act as an environmental pressure factor with implications for BDNF DNA methylation.
慢性应激的表观遗传影响:高危专业人员BDNF外显子IV基因甲基化
压力的特点是由压力源引起的体内平衡不平衡。当面对压力源时,身体会激活自主神经系统、免疫系统和下丘脑-垂体-肾上腺轴来恢复体内平衡。反复暴露在压力条件下会导致表观遗传变化。高压职业中与工作相关的压力源可以影响涉及脑功能的关键基因的表观遗传学,包括BDNF。本研究探讨了军警BDNF DNA甲基化与应激的关系。来自巴西ES Grande Metropolitan Region Vitória的123名军事警察被招募,通过对BDNF外显子IV启动子区域进行焦磷酸测序来评估应激是否影响甲基化。采用广义线性模型分析应激对甲基化水平的影响,控制了重要的混杂因素。结果表明,应激与BDNF外显子IV中CpG 5、CpG 6和CpG 11位点的DNA甲基化显著相关,该区域包括转录因子CREB的结合位点。这些结果表明,与没有经历过压力的宪兵相比,承受压力的宪兵在CpG 5、CpG 6和CpG 11时出现较高水平甲基化的几率分别高出0.259倍、0.471倍和0.461倍。基于这些发现,我们认为压力可能是影响BDNF DNA甲基化的环境压力因素。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Journal of psychiatric research
Journal of psychiatric research 医学-精神病学
CiteScore
7.30
自引率
2.10%
发文量
622
审稿时长
130 days
期刊介绍: Founded in 1961 to report on the latest work in psychiatry and cognate disciplines, the Journal of Psychiatric Research is dedicated to innovative and timely studies of four important areas of research: (1) clinical studies of all disciplines relating to psychiatric illness, as well as normal human behaviour, including biochemical, physiological, genetic, environmental, social, psychological and epidemiological factors; (2) basic studies pertaining to psychiatry in such fields as neuropsychopharmacology, neuroendocrinology, electrophysiology, genetics, experimental psychology and epidemiology; (3) the growing application of clinical laboratory techniques in psychiatry, including imagery and spectroscopy of the brain, molecular biology and computer sciences;
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