Social dominance predicts hippocampal glucocorticoid receptor recruitment and resilience to prenatal adversity

Moshe Gross,Ayala Miller,Albert Pinhasov,Hava Romi

doi:10.1038/s41598-018-27988-9

Moshe Gross, Ayala Miller + Show 2 more

Open Access

https://doi.org/10.1038/s41598-018-27988-9

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Journal: Scientific Reports	Publication Date: Jun 25, 2018
Citations: 25	License type: open-access

Affiliation: Ariel University

Abstract

The developing fetus is highly sensitive to prenatal stress, which may alter Hypothalamic-Pituitary-Adrenal (HPA) axis programming and increase the risk of behavioral disorders. There is high variability among the human population, wherein many offspring of stressed pregnancies display resilience to adversity, while the remainder displays vulnerability. In order to identify biological substrates mediating between resilience or vulnerability to prenatal adversity, we exposed stress-resistant Dominant (Dom) and stress-sensitive Submissive (Sub) mice to mild prenatal restraint stress (PRS, 45 min on gestational days (GD) 15, 16 and 17). We hypothesized that PRS would differentially alter prenatal programming of limbic regions regulating the HPA axis and affect among Dom and Sub offspring. Indeed, PRS increased Sub offspring’s serum corticosterone, and exaggerated their anxiety- and depressive-like behavior, while Dom offspring remained resilient to the hormonal and behavioral consequences of PRS. Moreover, PRS exposure markedly facilitated glucocorticoid receptor (GR) recruitment to the hippocampus among Dom mice in response to restraint stress, which may be responsible for their resilience to stressful challenge. These findings suggest proclivity to adaptive or maladaptive prenatal programming of hippocampal GR recruitment to be inheritable and predictable by social dominance or submissiveness.

Highlights

The developing fetus is highly sensitive to changes in the intra-uterine environment, which may carry life-long consequences for the offspring
Sub offspring of Prenatal Stress (PRS) pregnancies demonstrate heightened depressive-like behavior in the Dominant-Submissive Relationship (DSR) test
Sub offspring of prenatal restraint stress (PRS) pregnancies demonstrated heightened depressive-like behavior in the Forced Swim Test (FST)

Summary

Introduction

The developing fetus is highly sensitive to changes in the intra-uterine environment, which may carry life-long consequences for the offspring. Prenatal stress is an independent risk factor for psychiatric illness among adult offspring[19], there is high variability in the stress response among the human population: whereas many offspring of stressed pregnancies display resilience[20], the remainder may later develop affective disorders[21]. The variable response to prenatal stress and subsequent stressful challenge later in life are likely to be mediated by genetic variation[22], such that networks of gene-environment interactions may underlie the highly unpredictable effects of a pregnancy challenged by stress[23]. In order to determine the mechanisms underlying resilience and sensitivity to prenatal stress, the present study made use of selectively bred stress-resilient Dominant (Dom)[24,25] and stress-sensitive Submissive (Sub) mice[26,27]. Adult male offspring were analyzed for depressive- and anxiety-like behavior, as well as their HPA axis regulation under both basal conditions and in response to acute stress

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