DNA methylation as a risk factor in the effects of early life stress.
DNA methylation as a risk factor in the effects of early life stress.
复制标题
DOI：
10.1016/j.bbi.2011.05.001
复制
发表时间：
2011-11
影响因子：
15.1
通讯作者：
Mann, J. John
中科院分区：
文献类型：
--
作者：
Kinnally, Erin L.;Feinberg, Caroline;Kim, David;Ferguson, Kerel;Leibel, Rudolph;Coplan, Jeremy D.;Mann, J. John
关键词：
特定基因调控区域内的表观遗传标记(如DNA 5-甲基胞嘧啶[5mC]含量或CpG甲基化)已被证明在应激适应和早期逆境后导致的健康轨迹中发挥不同的作用。然而，表观基因组绝大多数的发育规划尚未确定，其在早期应激的影响中的作用也基本不清楚。在本研究中，我们在一个非人类灵长类动物模型中研究了早期生活应激、全表观基因组和候选应激途径基因(5-HTT)甲基化模式与成年行为应激适应的关系。在生命早期，将实验可变觅食需求(VFD)应激或对照条件施加给两组，每组10只雌性短尾猴(Macaca Radiata)及其母亲。作为成年人(3-13岁)，这些女性被评估了在四种强度增加的条件下对压力的行为适应。用亚硫酸氢钠焦磷酸测序法测定全血DNA 5-HTT 5mC状态，用ELISA法测定总5mC含量。无论是应激反应还是DNA甲基化都不同于早期的生活压力。然而，我们发现，较高的5-HTT和全基因组5mC都与早期生活应激后行为应激反应增强有关，但与对照条件无关。因此，无论发育起源如何，在早期应激的背景下，较高的DNA甲基化水平会带来“风险”的基因组背景。我们认为，这可能是由于发育早期应激适应所需基因表达的可塑性受到限制。这种风险可能会对心理和身体压力适应和健康产生更广泛的影响。
Epigenetic marks (eg, DNA 5-methylcytosine [5mC] content or CpG methylation) within specific gene regulatory regions have been demonstrated to play diverse roles in stress adaptation and resulting health trajectories following early adversity. Yet the developmental programming of the vast majority of the epigenome has not yet been characterized, and its role in the impact of early stress largely unknown. In the present study, we investigated the relationships among early life stress, whole-epigenome and candidate stress pathway gene (serotonin transporter, 5-HTT) methylation patterns, and adult behavioral stress adaptation in a non-human primate model. Early in life, experimental variable foraging demand (VFD) stress or control conditions were administered to two groups each of 10 female bonnet macaques (Macaca radiata) and their mothers. As adults (3–13 years of age), these females were assessed for behavioral adaptation to stress across four conditions of increasing intensity. Blood DNA 5-HTT 5mC status was determined using sodium bisulfite pyrosequencing and total 5mC content was determined using ELISA. Neither stress reactivity nor DNA methylation differed based on early life stress. However, we found that both greater 5-HTT and whole-genome 5mC was associated with enhanced behavioral stress reactivity following early life stress, but not control conditions. Therefore, regardless of developmental origin, greater DNA methylation conferred a genomic background of “risk” in the context of early stress. We suggest that this may arise from constrained plasticity in gene expression needed for stress adaptation early in development. This risk may have wider implications for psychological and physical stress adaptation and health.
登录
查看更多内容
影响因子：
9.8
作者：
Schalkwyk, Leonard C.;Meaburn, Emma L.;Mill, Jonathan
通讯作者：
Mill, Jonathan
DOI：
10.1523/jneurosci.1758-09.2009
发表时间：
2009-09-16
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Covington HE 3rd;Maze I;LaPlant QC;Vialou VF;Ohnishi YN;Berton O;Fass DM;Renthal W;Rush AJ 3rd;Wu EY;Ghose S;Krishnan V;Russo SJ;Tamminga C;Haggarty SJ;Nestler EJ
通讯作者：
Nestler EJ
影响因子：
120.7
作者：
Risch, Neil;Herrell, Richard;Lehner, Thomas;Liang, Kung-Yee;Eaves, Lindon;Hoh, Josephine;Griem, Andrea;Kovacs, Maria;Ott, Jurg;Merikangas, Kathleen Ries
通讯作者：
Merikangas, Kathleen Ries
DOI：
10.1073/pnas.93.4.1619
发表时间：
1996-02-20
影响因子：
11.1
作者：
Coplan, JD;Andrews, MW;Nemeroff, CB
通讯作者：
Nemeroff, CB
影响因子：
3.7
作者：
Oberlander, Tim F.;Weinberg, Joanne;Devlin, Angela M.
通讯作者：
Devlin, Angela M.