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.

Maternal High Fat Diet-Induced Obesity Modifies Histone Binding and Expression of Oxtr in Offspring Hippocampus in a Sex-Specific Manner

“…These neuropeptides signal via their cognate G protein-coupled receptors, arginine vasopressin 1A (Avpr1a) and oxytocin receptor (Oxtr), to modulate diverse aspects of human social behavior, and dysfunction of these systems are well established in neurodevelopmental disorders [17,18,19]. In addition, there is evidence that epigenetic regulation of Avpr1a and Oxtr expression may be particularly sensitive to environmental disruption during critical periods of development [20,21], and post translational modifications to histone tails is one of the major epigenetic processes regulating the transcription of G-protein coupled receptors in the brain [22]. Late prenatal life (e.g., GD 17.5 in the mouse) is one such critical period where we and others have already observed several changes both to fetal physiology [23] and developmental changes to multiple cell types in multiple brain regions [12,24,25,26,27].…”

A Review of Oxytocin and Arginine-Vasopressin Receptors and Their Modulation of Autism Spectrum Disorder

“…Beyond the fetal period, environmental factors have also been found to induce epigenetic changes. For instance, intense social experiences in sensitive life stages can have enduring influences not only on behavior, but also on AVPR1a gene expression in the hippocampal region through a change in patterns of methylation (Bodden et al, 2017 ).…”

Varying Social Experiences in Adulthood Do Not Differentially Affect Anxiety-Like Behavior But Stress Hormone Levels

“…In adulthood, on the other hand, developmental plasticity is lower due to progressed brain maturation (Rice and Barone, 2000 ). Despite this, however, it has been shown that social experience can still modulate emotional behavior and underlying patterns of gene expression in adult rodents (Buwalda et al, 2005 ; Jansen et al, 2010 ; Bodden et al, 2017 ). In fact, also in the mentioned studies on the “coping with challenge” effect escapable adversity was experienced in early adulthood (Bodden et al, 2015 , 2017 ; Remmes et al, 2016 ).…”

“…Despite this, however, it has been shown that social experience can still modulate emotional behavior and underlying patterns of gene expression in adult rodents (Buwalda et al, 2005 ; Jansen et al, 2010 ; Bodden et al, 2017 ). In fact, also in the mentioned studies on the “coping with challenge” effect escapable adversity was experienced in early adulthood (Bodden et al, 2015 , 2017 ; Remmes et al, 2016 ). The results of the present investigation in combination with our previous findings, however, suggest that for the occurrence of the “coping with challenge” effect specific social experiences have to be made already during early phases of life when brain circuits are highly plastic.…”

“…This finding was confirmed in a follow-up study (Remmes et al, 2016 ). Additionally, a second follow-up study revealed corresponding differences in the expression of genes associated with anxiety and stress circuits (Bodden et al, 2017 ). Altogether, these results gave rise to the formulation of the “coping with challenge” hypothesis.…”