Mild Prenatal Stress Causes Emotional and Brain Structural Modifications in Rats of Both Sexes.

Carina Soares-Cunha,Bárbara Coimbra,Deolinda Silva,Ana João Rodrigues,Sónia Borges,Ana Verónica Domingues,Nuno Sousa

doi:10.3389/fnbeh.2018.00129

Carina Soares-Cunha, Bárbara Coimbra + Show 5 more

Open Access

https://doi.org/10.3389/fnbeh.2018.00129

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Abstract

Stress or high levels of glucocorticoids (GCs) during developmental periods is known to induce persistent effects in the neuroendocrine circuits that control stress response, which may underlie individuals’ increased risk for developing neuropsychiatric conditions later in life, such as anxiety or depression. We developed a rat model (Wistar han) of mild exposure to unpredictable prenatal stress (PS), which consists in a 4-h stressor administered three times per week on a random basis; stressors include strobe lights, noise and restrain. Pregnant dams subjected to this protocol present disrupted circadian corticosterone secretion and increased corticosterone secretion upon acute stress exposure. Regarding progeny, both young adult (2 months old) male and female rats present increased levels of circulating corticosterone and hyperactivity of the hypothalamus-pituitary-adrenal axis to acute stress exposure. Both sexes present anxious- and depressive-like behaviors, shown by the decreased time spent in the open arms of the elevated plus maze (EPM) and in the light side of the light-dark box (LDB), and by increased immobility time in the forced swim test, respectively. Interestingly, these results were accompanied by structural modifications of the bed nucleus of stria terminalis (BNST) and hippocampus, as well as decreased norepinephrine and dopamine levels in the BNST, and serotonin levels in the hippocampus. In summary, we characterize a new model of mild PS, and show that stressful events during pregnancy can lead to long-lasting structural and neurochemical effects in the offspring, which affect behavior in adulthood.

Highlights

Life adversity, including physical and emotional neglect and traumatic experiences, can induce persistent effects on physical and mental health in both animal models and humans (Heim and Nemeroff, 2001; Teicher et al, 2003)
The predicted incidence of such disturbances is much lower in individuals abused as adults (Brown and Moran, 1994; McCauley et al, 1997), a finding that points to the existence of critical time windows during which the organism is sensitive to stress-induced pathology later in life
The MR are important in the recognition of the stress and the onset of the stress response whereas GC receptors (GR) are activated by the presence of abnormally high levels of corticosterone and are important in the cessation of the stress reaction

Summary

Introduction

Life adversity, including physical and emotional neglect and traumatic experiences, can induce persistent effects on physical and mental health in both animal models and humans (Heim and Nemeroff, 2001; Teicher et al, 2003). In utero exposure to GC/stress has been found to be associated with long-lasting deficits in mood and affective, as well as addictive behaviors in humans (Heim and Nemeroff, 2001; Sinha, 2001; Malaspina et al, 2008) and in animal models (Oliveira et al, 2006; Mabandla et al, 2008; Markham et al, 2010; Rodrigues et al, 2012; Borges et al, 2013a,b; SoaresCunha et al, 2014). We have shown that prenatal GCs exposure induces long lasting epigenetic changes in dopamine receptor D2 (Rodrigues et al, 2012)

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