Lux Vanessa
Department of Genetic Psychology, Faculty of Psychology, Ruhr University Bochum, Bochum, Germany.
Curr Genomics. 2018 Dec;19(8):638-652. doi: 10.2174/1389202919666180307151358.
Epigenetic processes during early brain development can function as 'developmental switches' that contribute to the stability of long-term effects of early environmental influences by programming central feedback mechanisms of the HPA axis and other neural networks. In this thematic review, we summarize accumulated evidence for a dual-activation of stress-related and sensory networks underlying the epigenetic programming effects of early life stress. We discuss findings indicating epigenetic programming of stress-related genes with impact on HPA axis function, the interaction of epigenetic mechanisms with neural activity in stress-related neural networks, epigenetic effects of glucocorticoid exposure, and the impact of stress on sensory development. Based on these findings, we propose that the combined activation of stress-related neural networks and stressor-specific sensory networks leads to both neural and hormonal priming of the epigenetic machinery, which sensitizes these networks for developmental programming effects. This allows stressor-specific adaptations later in life, but may also lead to functional mal-adaptations, depending on timing and intensity of the stressor. Finally, we discuss methodological and clinical implications of the dual-activation hypothesis. We emphasize that, in addition to modifications in stress-related networks, we need to account for functional modifications in sensory networks and their epigenetic underpinnings to elucidate the long-term effects of early life stress.
早期大脑发育过程中的表观遗传过程可充当“发育开关”，通过对下丘脑-垂体-肾上腺（HPA）轴及其他神经网络的中枢反馈机制进行编程，促进早期环境影响的长期效应的稳定性。在这篇专题综述中，我们总结了有关早期生活应激的表观遗传编程效应背后应激相关网络和感觉网络双重激活的累积证据。我们讨论了相关研究结果，这些结果表明应激相关基因的表观遗传编程对HPA轴功能有影响，表观遗传机制与应激相关神经网络中的神经活动相互作用，糖皮质激素暴露的表观遗传效应，以及应激对感觉发育的影响。基于这些发现，我们提出应激相关神经网络和应激源特异性感觉网络的联合激活会导致表观遗传机制在神经和激素方面的启动，从而使这些网络对发育编程效应敏感。这使得个体在生命后期能够对应激源产生特异性适应，但也可能导致功能适应不良，这取决于应激源的时机和强度。最后，我们讨论了双重激活假说的方法学和临床意义。我们强调，除了应激相关网络的改变外，我们还需要考虑感觉网络的功能改变及其表观遗传基础，以阐明早期生活应激的长期影响。
