Aberrant Early in Life Stimulation of the Stress-Response System Affects Emotional Contagion and Oxytocin Regulation in Adult Male Mice.

Giovanni Laviola,Marco Fiore,Carla Petrella,Ludovica Busdraghi

doi:10.3390/ijms22095039

Abstract

Results over the last decades have provided evidence suggesting that HPA axis dysfunction is a major risk factor predisposing to the development of psychopathological behaviour. This susceptibility can be programmed during developmental windows of marked neuroplasticity, allowing early-life adversity to convey vulnerability to mental illness later in life. Besides genetic predisposition, also environmental factors play a pivotal role in this process, through embodiment of the mother’s emotions, or via nutrients and hormones transferred through the placenta and the maternal milk. The aim of the current translational study was to mimic a severe stress condition by exposing female CD-1 mouse dams to abnormal levels of corticosterone (80 µg/mL) in the drinking water either during the last week of pregnancy (PreCORT) or the first one of lactation (PostCORT), compared to an Animal Facility Rearing (AFR) control group. When tested as adults, male mice from PostCORT offspring and somewhat less the PreCORT mice exhibited a markedly increased corticosterone response to acute restraint stress, compared to perinatal AFR controls. Aberrant persistence of adolescence-typical increased interest towards novel social stimuli and somewhat deficient emotional contagion also characterised profiles in both perinatal-CORT groups. Intranasal oxytocin (0 or 20.0 µg/kg) generally managed to reduce the stress response and restore a regular behavioural phenotype. Alterations in density of glucocorticoid and mineralocorticoid receptors, oxytocin and µ- and κ-opioid receptors were found. Changes differed as a function of brain areas and the specific age window of perinatal aberrant stimulation of the HPA axis. Present results provided experimental evidence in a translational mouse model that precocious adversity represents a risk factor predisposing to the development of psychopathological behaviour.

Highlights

Introduction iationsBeside genetic background, an immature organism acquires developmental plasticity, basically through epigenetic modifications, since the very first phases of life, to rapidly adapt its phenotype in response to external environmental cues
All behavioural data refer to animals pertaining to arm 1, while molecular analyses were performed on subjects assigned to arm 2 (Figure 1)
Hypothalamus: glucocorticoid receptors resulted to be significantly reduced as a consequence of perinatal treatment (F2,17 = 7.555, p = 0.005): Prenatal CORT (PreCORT) and PostCORT presented lower levels of receptors than Animal Facility Rearing (AFR) group (Figure 13b)

Summary

Introduction

An immature organism acquires developmental plasticity, basically through epigenetic modifications, since the very first phases of life, to rapidly adapt its phenotype in response to external environmental cues. The latter are relevant to the probable environment the mature organism will have to face, in order to optimize the chances of survival [1,2]. This adaptation may occur at the expense of a predisposition for stress-related diseases and psychiatric disorders (in humans), which may present clinical manifestations at different ages [3,4,5,6]. Premature and marked activation of the stress axis, during early ontogenetic windows in the offspring

Methods

Results

Discussion

Conclusion