研究人员发现，生命早期所遭遇的严重压力可能会导致小鼠基因表达模式的长久变化，新成果发表在11月在线出版的《自然—神经学》期刊上。
以前的研究显示，在压力或创伤环境中长大的儿童，在之后的生命岁月中患抑郁的风险更高。为阐明其背后的神经生物学机制，Dietmar Spengler和同事对小鼠进行了研究，在其出生的头十天中，这些小鼠被迫频繁与母亲分离。这是一种充满压力的分离状态，导致了负责编码压力相关荷尔蒙AVP的基因上的一种特别抑制机制的缺失，并最终导致这种荷尔蒙水平的升高。
在这种压力状态发生后一年，Spengler和同事依然在这种小鼠体内发现了不正常的基因修饰、AVP水平的升高，以及面对压力环境时过度的精神反应。他们认为，这种源自早期生活压力的行动和精神状态的长期存在，部分原因可能应归咎于大脑中基因调控的持久变化。（生物谷Bioon.com）
生物谷推荐原始出处：
Nature Neuroscience 12, 1559 - 1566 (2009) 8 November 2009 | Corrected online: 3 December 2009 | doi:10.1038/nn.2436
Dynamic DNA methylation programs persistent adverse effects of early-life stress
Chris Murgatroyd1, Alexandre V Patchev1, Yonghe Wu1, Vincenzo Micale1, Yvonne Bockmühl1, Dieter Fischer1, Florian Holsboer1, Carsten T Wotjak1, Osborne F X Almeida1 & Dietmar Spengler1
Adverse early life events can induce long-lasting changes in physiology and behavior. We found that early-life stress (ELS) in mice caused enduring hypersecretion of corticosterone and alterations in passive stress coping and memory. This phenotype was accompanied by a persistent increase in arginine vasopressin (AVP) expression in neurons of the hypothalamic paraventricular nucleus and was reversed by an AVP receptor antagonist. Altered Avp expression was associated with sustained DNA hypomethylation of an important regulatory region that resisted age-related drifts in methylation and centered on those CpG residues that serve as DNA-binding sites for the methyl CpG–binding protein 2 (MeCP2). We found that neuronal activity controlled the ability of MeCP2 to regulate activity-dependent transcription of the Avp gene and induced epigenetic marking. Thus, ELS can dynamically control DNA methylation in postmitotic neurons to generate stable changes in Avp expression that trigger neuroendocrine and behavioral alterations that are frequent features in depression.
Max Planck Institute of Psychiatry, Munich, Germany.
