Early life adversity and serotonin transporter gene variation interact to affect DNA methylation of the corticotropin-releasing factor gene promoter region in the adult rat brain
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Publication year
2015Author(s)
Number of pages
13 p.
Source
Development and Psychopathology, 27, 1, (2015), pp. 123-135ISSN
Publication type
Article / Letter to editor
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Organization
Anatomy
Cognitive Neuroscience
Neurophysiology
Journal title
Development and Psychopathology
Volume
vol. 27
Issue
iss. 1
Languages used
English (eng)
Page start
p. 123
Page end
p. 135
Subject
Neurophysiology; Radboudumc 13: Stress-related disorders DCMN: Donders Center for Medical Neuroscience; Radboudumc 1: Alzheimer`s disease DCMN: Donders Center for Medical NeuroscienceAbstract
The interaction between childhood maltreatment and the serotonin transporter (5-HTT) gene linked polymorphic region has been associated with increased risk to develop major depression. This Gene x Environment interaction has furthermore been linked with increased levels of anxiety and glucocorticoid release upon exposure to stress. Both endophenotypes are regulated by the neuropeptide corticotropin-releasing factor (CRF) or hormone, which is expressed by the paraventricular nucleus of the hypothalamus, the bed nucleus of the stria terminalis, and the central amygdala (CeA). Therefore, we hypothesized that altered regulation of the expression of CRF in these areas represents a major neurobiological mechanism underlying the interaction of early life stress and 5-HTT gene variation. The programming of gene transcription by Gene x Environment interactions has been proposed to involve epigenetic mechanisms such as DNA methylation. In this study, we report that early life stress and 5-HTT genotype interact to affect DNA methylation of the Crf gene promoter in the CeA of adult male rats. Furthermore, we found that DNA methylation of a specific site in the Crf promoter significantly correlated with CRF mRNA levels in the CeA. Moreover, CeA CRF mRNA levels correlated with stress coping behavior in a learned helplessness paradigm. Together, our findings warrant further investigation of the link of Crf promoter methylation and CRF expression in the CeA with behavioral changes that are relevant for psychopathology.
This item appears in the following Collection(s)
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- Electronic publications [122512]
- Faculty of Medical Sciences [90359]
- Faculty of Science [34989]
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