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Impact of varying social experiences during life history on behaviour, gene expression, and vasopressin receptor gene methylation in mice.

ABSTRACT: Both negative and positive social experiences during sensitive life phases profoundly shape brain and behaviour. Current research is therefore increasingly focusing on mechanisms mediating the interaction between varying life experiences and the epigenome. Here, male mice grew up under either adverse or beneficial conditions until adulthood, when they were subdivided into groups exposed to situations that either matched or mismatched previous conditions. It was investigated whether the resulting four life histories were associated with changes in anxiety-like behaviour, gene expression of selected genes involved in anxiety and stress circuits, and arginine vasopressin receptor 1a (Avpr1a) gene methylation. Varying experiences during life significantly modulated (1) anxiety-like behaviour; (2) hippocampal gene expression of Avpr1a, serotonin receptor 1a (Htr1a), monoamine oxidase A (Maoa), myelin basic protein (Mbp), glucocorticoid receptor (Nr3c1), growth hormone (Gh); and (3) hippocampal DNA methylation within the Avpr1a gene. Notably, mice experiencing early beneficial and later adverse conditions showed a most pronounced downregulation of Avpr1a expression, accompanied by low anxiety-like behaviour. This decrease in Avpr1a expression may have been, in part, a consequence of increased methylation in the Avpr1a gene. In summary, this study highlights the impact of interactive social experiences throughout life on the hippocampal epigenotype and associated behaviour.

SUBMITTER: Bodden C

PROVIDER: S-EPMC5562890 | biostudies-other | 2017 Aug

REPOSITORIES: biostudies-other

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Impact of varying social experiences during life history on behaviour, gene expression, and vasopressin receptor gene methylation in mice.

Bodden Carina C van den Hove Daniel D Lesch Klaus-Peter KP Sachser Norbert N

Scientific reports 20170818 1

Both negative and positive social experiences during sensitive life phases profoundly shape brain and behaviour. Current research is therefore increasingly focusing on mechanisms mediating the interaction between varying life experiences and the epigenome. Here, male mice grew up under either adverse or beneficial conditions until adulthood, when they were subdivided into groups exposed to situations that either matched or mismatched previous conditions. It was investigated whether the resulting ...[more]

PMID: 28821809

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Project description:BackgroundSocial anxiety disorder is characterized by intense fear and avoidance of social interactions and scrutiny by others. Although alterations in attentional control seem to play a central role in the psychopathology of social anxiety disorder, the neural underpinnings in prefrontal brain regions have not yet been fully clarified.MethodsThe present study used functional MRI in participants (age 18-50 yr) with social anxiety disorder (n = 42, 31 female) and without (n = 58, 33 female). It investigated the interrelation of the effects of social anxiety disorder and early-life adversity (a main environmental risk factor of social anxiety disorder) on brain activity during an attentional control task. We applied DNA methylation analysis to determine whether epigenetic modulation in the gene encoding the glucocorticoid receptor, NR3C1, might play a mediating role in this process.ResultsWe identified 2 brain regions in the left and medial prefrontal cortex that exhibited an interaction effect of social anxiety disorder and early-life adversity. In participants with low levels of early-life adversity, neural activity in response to disorder-related stimuli was increased in association with social anxiety disorder. In participants with high levels of early-life adversity, neural activity was increased only in participants without social anxiety disorder. NR3C1 DNA methylation partly mediated the effect of social anxiety disorder on brain activity as a function of early-life adversity.LimitationsThe absence of behavioural correlates associated with social anxiety disorder limited functional interpretation of the results.ConclusionThese findings demonstrate that the neurobiological processes that underlie social anxiety disorder might be fundamentally different depending on experiences of early-life adversity. Long-lasting effects of early-life adversity might be encoded in NR3C1 DNA methylation and entail alterations in social anxiety disorder-related activity patterns in the neural network of attentional control.

Dataset Information

Impact of varying social experiences during life history on behaviour, gene expression, and vasopressin receptor gene methylation in mice.

Publications

Impact of varying social experiences during life history on behaviour, gene expression, and vasopressin receptor gene methylation in mice.

Similar Datasets

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