Lundgaard Donovan Lene, Henningsen Kim, Flou Kristensen Anne, Wiborg Ove, Nieland John Dirk, Lichota Jacek
Neurobiology Research and Drug Delivery Group, Department of Health Science and Technology, Aalborg University, 9220 Aalborg Øst, Denmark.
Department of Biomedicine-Dandrite, Takeuchi Team, Aarhus University, 8000 Aarhus C, Denmark.
J Pers Med. 2021 Mar 16;11(3):209. doi: 10.3390/jpm11030209.
Depression is one of the most prevalent mental diseases worldwide. Patients with psychiatric diseases often have a history of childhood neglect, indicating that early-life experiences predispose to psychiatric diseases in adulthood. Two strong models were used in the present study: the maternal separation/early deprivation model (MS) and the chronic mild stress model (CMS). In both models, we found changes in the expression of a number of genes such as and . Strikingly, there was a clear regulation of expression of four genes involved in the AP-1 complex: , , , and . Interestingly, different expression levels were observed depending on the model, whereas the combination of the models resulted in a normal level of gene expression. The effects of MS and CMS on gene expression were associated with distinct histone methylation/acetylation patterns of all four genes. The epigenetic changes, like gene expression, were also dependent on the specific stressor or their combination. The obtained results suggest that single life events leave a mark on gene expression and the epigenetic signature of gene promoters, but a combination of different stressors at different life stages can further change gene expression through epigenetic factors, possibly causing the long-lasting adverse effects of stress.
抑郁症是全球最常见的精神疾病之一。患有精神疾病的患者往往有童年被忽视的经历，这表明早期生活经历易导致成年后患精神疾病。本研究使用了两种强大的模型：母婴分离/早期剥夺模型（MS）和慢性轻度应激模型（CMS）。在这两种模型中，我们发现了许多基因如 和 的表达变化。引人注目的是，参与AP-1复合体的四个基因 、 、 和 的表达有明显的调控。有趣的是，根据模型不同观察到了不同的表达水平，而模型的组合导致基因表达水平正常。MS和CMS对基因表达的影响与所有四个基因不同的组蛋白甲基化/乙酰化模式有关。表观遗传变化，如基因表达，也取决于特定的应激源或它们的组合。获得的结果表明，单一的生活事件会在基因表达和基因启动子的表观遗传特征上留下印记，但不同生命阶段不同应激源的组合可通过表观遗传因素进一步改变基因表达，可能导致应激的长期不良影响。
