Maternal separation alters nerve growth factor and corticosterone levels but not the DNA methylation status of the exon 1(7) glucocorticoid receptor promoter region.

Maternal separation alters nerve growth factor and corticosterone levels but not the DNA methylation status of the exon 1(7) glucocorticoid receptor promoter region.
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DOI:
10.1007/s11011-009-9163-4
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发表时间:
2009-12
影响因子:
3.6
通讯作者:
Stein, D. J.
Stein, D. J.
中科院分区:
医学3区
文献类型:
--
作者:
Daniels, W. M. U.;Fairbairn, L. R.;van Tilburg, G.;McEvoy, C. R. E.;Zigmond, M. J.;Russell, V. A.;Stein, D. J.

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在生命早期将幼鼠与它们的母亲分开是一种常用的动物模型,用于研究焦虑和抑郁等精神疾病的发展。本研究调查了产妇分居期结束后多久,与上述疾病有关的行为和神经内分泌异常会出现。对SD大鼠幼鼠进行母体分离(从出生后第2天到第14天,每天3小时),并在7天后测定它们的行为和HPA轴活动。我们还测量了他们海马区的神经生长因子水平,并评估了该脑区糖皮质激素受体外显子17启动子区的DNA甲基化状态。早在不良事件结束后7天,就观察到与血浆皮质酮释放增加和海马区神经生长因子水平升高有关的行为变化。未观察到糖皮质激素受体外显子17启动子区甲基化状态的改变。我们的数据表明,早期的生活逆境可能导致异常行为的快速发展和HPA轴的失调,尽管外显子17糖皮质激素受体启动子区没有发生表观遗传变化。我们进一步认为,观察到的神经营养素水平的增加反映了试图对抗母体分离的长期有害影响的代偿机制。
Separating rat pups from their mothers during the early stages of life is an animal model commonly used to study the development of psychiatric disorders such as anxiety and depression. The present study investigated how soon after the termination of the maternal separation period behavioural and neuroendocrine abnormalities relevant to above-mentioned illnesses would manifest. Sprague Dawley rat pups were subjected to maternal separation (3 hours per day from postnatal day 2 through 14) and their behaviour and HPA axis activity determined 7 days later. We also measured nerve growth factor levels in their hippocampi and assessed the DNA methylation status of the promoter region of exon 17 of the glucocorticoid receptor in this brain region. As early as 7 days after the termination of the adverse event, a change in behaviour was observed that was associated with increased plasma corticosterone release and elevated nerve growth factor levels in the hippocampus. No alteration in the methylation status of the exon 17 glucocorticoid receptor promoter region was observed. Our data indicate that early life adversity may lead to the rapid development of abnormal behaviours and HPA axis dysregulation though no epigenetic changes to the exon 17 glucocorticoid receptor promoter region occurred. We further propose that the observed increased neurotrophin levels reflect compensatory mechanisms that attempt to combat the long-term deleterious effects of maternal separation.
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