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母亲在怀孕期间吸烟与青少年后代脑源性神经营养因子-6 外显子的表观遗传修饰有关。

Maternal smoking during pregnancy is associated with epigenetic modifications of the brain-derived neurotrophic factor-6 exon in adolescent offspring.

机构信息

Brain and Body Centre, University of Nottingham, Nottingham, UK.

出版信息

Am J Med Genet B Neuropsychiatr Genet. 2010 Oct 5;153B(7):1350-4. doi: 10.1002/ajmg.b.31109.

DOI:10.1002/ajmg.b.31109
PMID:20583129
Abstract

Prenatal exposure to maternal cigarette smoking (PEMCS) is associated with variations in brain and behavior in adolescence. Epigenetic mechanisms may mediate some of the consequences of PEMCS through methylation of deoxyribonucleic acid (DNA) in genes important for brain development, such as the brain-derived neurotrophic factor (BDNF). In the current study, we used bisulfite sequencing to assess DNA methylation of the BDNF promoter in the blood of adolescents whose mothers smoked during pregnancy. We demonstrate that PEMCS is associated with higher rates of DNA methylation in the BDNF-6 exon. These results suggest that PEMCS may lead to long-term down-regulation of BDNF expression via the increase of DNA methylation in its promoter region. Such mechanisms could, in turn, lead to modifications in both development and plasticity of the brain exposed in utero to maternal cigarette smoking.

摘要

产前暴露于母体吸烟(PEMCS)与青少年时期的大脑和行为变化有关。表观遗传机制可能通过对大脑发育相关基因(如脑源性神经营养因子(BDNF))中的脱氧核糖核酸(DNA)进行甲基化,从而介导 PEMCS 的一些后果。在目前的研究中,我们使用亚硫酸氢盐测序来评估在其启动子区域的 DNA 甲基化,这些结果表明 PEMCS 可能导致 BDNF 表达的长期下调,从而导致大脑在子宫内暴露于母体吸烟时的发育和可塑性发生改变。

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