Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology, University of Bristol, Dorothy Hodgkin Building, Whitson Street, Bristol BS1 3NY, United Kingdom.
Brain Behav Immun. 2011 Oct;25(7):1305-15. doi: 10.1016/j.bbi.2011.06.005. Epub 2011 Jun 14.
Epigenetic mechanisms are processes at the level of the chromatin that control the expression of genes but their role in neuro-immuno-endocrine communication is poorly understood. This review focuses on epigenetic modifications induced by a range of stressors, both physical and psychological, and examines how these variations can affect the biological activity of cells. It is clear that epigenetic modifications are critical in explaining how environmental factors, which have no effect on the DNA sequence, can have such profound, long-lasting influences on both physiology and behavior. A signaling pathway involving activation of MEK-ERK1/2, MSK1, and Elk-1 signaling molecules has been identified in the hippocampus which results in the phospho-acetylation of histone H3 and modification of gene expression including up-regulation of immediate early genes such as c-Fos. This pathway can be induced by a range of challenging experiences including forced swimming, Morris water maze learning, fear conditioning and exposure to the radial maze. Glucocorticoid (GC) hormones, released as part of the stress response and acting via glucocorticoid receptors (GRs), enhance signaling through the ERK1/2/MSK1-Elk-1 pathway and thereby increase the impact on epigenetic and gene expression mechanisms. The role of synergetic interactions between these pathways in adaptive responses to stress and learning and memory paradigms is discussed, in addition we speculate on their potential role in immune function.
表观遗传机制是在染色质水平上控制基因表达的过程，但它们在神经免疫内分泌通讯中的作用还知之甚少。这篇综述重点介绍了一系列物理和心理应激源诱导的表观遗传修饰，并探讨了这些变化如何影响细胞的生物学活性。很明显，表观遗传修饰对于解释环境因素如何在没有影响 DNA 序列的情况下对生理和行为产生如此深远和持久的影响至关重要。在海马体中已经确定了一条涉及 MEK-ERK1/2、MSK1 和 Elk-1 信号分子激活的信号通路，导致组蛋白 H3 的磷酸化乙酰化和基因表达的修饰，包括立即早期基因如 c-Fos 的上调。这条通路可以通过一系列具有挑战性的体验来诱导，包括强迫游泳、莫里斯水迷宫学习、恐惧条件反射和暴露于放射状迷宫。糖皮质激素（GC）激素作为应激反应的一部分释放，通过糖皮质激素受体（GRs）发挥作用，增强 ERK1/2/MSK1-Elk-1 通路的信号传递，从而增加对表观遗传和基因表达机制的影响。本文还讨论了这些途径之间协同相互作用在应激和学习记忆范式中的适应性反应中的作用，并推测它们在免疫功能中的潜在作用。
