研究人員發(fā)現(xiàn),，生命早期所遭遇的嚴(yán)重壓力可能會(huì)導(dǎo)致小鼠基因表達(dá)模式的長(zhǎng)久變化,，新成果發(fā)表在11月在線出版的《自然—神經(jīng)學(xué)》期刊上。
以前的研究顯示，在壓力或創(chuàng)傷環(huán)境中長(zhǎng)大的兒童,，在之后的生命歲月中患抑郁的風(fēng)險(xiǎn)更高,。為闡明其背后的神經(jīng)生物學(xué)機(jī)制，Dietmar Spengler和同事對(duì)小鼠進(jìn)行了研究,，在其出生的頭十天中,，這些小鼠被迫頻繁與母親分離。這是一種充滿壓力的分離狀態(tài),，導(dǎo)致了負(fù)責(zé)編碼壓力相關(guān)荷爾蒙AVP的基因上的一種特別抑制機(jī)制的缺失,，并最終導(dǎo)致這種荷爾蒙水平的升高。
在這種壓力狀態(tài)發(fā)生后一年,，Spengler和同事依然在這種小鼠體內(nèi)發(fā)現(xiàn)了不正常的基因修飾,、AVP水平的升高，以及面對(duì)壓力環(huán)境時(shí)過度的精神反應(yīng),。他們認(rèn)為,，這種源自早期生活壓力的行動(dòng)和精神狀態(tài)的長(zhǎng)期存在，部分原因可能應(yīng)歸咎于大腦中基因調(diào)控的持久變化,。（生物谷Bioon.com）
生物谷推薦原始出處：
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.
