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Current Genomics


ISSN (Print): 1389-2029
ISSN (Online): 1875-5488

Review Article

Epigenetic Programming Effects of Early Life Stress: A Dual-Activation Hypothesis

Author(s): Vanessa Lux*

Volume 19, Issue 8, 2018

Page: [638 - 652] Pages: 15

DOI: 10.2174/1389202919666180307151358

open access plus


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 longterm effects of early life stress.

Keywords: Neuroepigenetics, Sensory development, HPA axis, Critical period, Bdnf, Mecp2.

Graphical Abstract

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