Short- and long-term effects of stress during adolescence on emotionality and HPA function of animals exposed to alcohol prenatally

Abstract

Prenatal alcohol exposure (PAE) is associated with extremely high rates of psychopathologies, which may be mediated by the hypothalamic-pituitary-adrenal (HPA) dysregulation observed in exposed individuals. Of relevance, PAE carries an increased risk of exposure to stressful environments throughout life. Importantly, stressful experiences during adolescence increase vulnerability to psychopathologies. However, little is known about how adolescent stressful experiences in the context of PAE-induced HPA dysregulation may further alter the developmental trajectory and potentially contribute to the disproportionally high rate of psychopathologies observed in this population. Here we investigate the short-and long-term effects of adolescent chronic mild stress (CMS) on the emergence of anxiety-/depressive-like behaviors (open-field and forced swim test - FST) and on HPA activity (corticosterone and type 1 CRH receptor – CRHR1) in PAE male and female rats. Under non-CMS conditions, open field results indicate that PAE induced inappropriate behavior (increased time in center) in males and females, with increased activity in female adolescents, but anxiety-like behavior in adult PAE females. Conversely, FST results indicate that PAE induced depressive-like behavior in adolescent males. Exposure to CMS resulted in increased activity in adolescent males and anxiety-like behaviors in adult females. Moreover, PAE and/or CMS altered corticosterone and CRHR1 expression in the mPFC and amygdala. Together, these results suggest that PAE and adolescent CMS induce dynamic neurobehavioral alterations that manifest differently depending on the age and sex of the animal. These results highlight the importance of using both sexes as well as an ontogenetic approach when investigating the effects of environmental adversity.

Effects of early-life adversity on immune function are mediated by prenatal environment: Role of prenatal alcohol exposure

“…Additionally, in the present study, PAE animals showed increased CRP levels compared to control animals, and PAE pups exposed to early-life adversity showed even higher levels of serum CRP. This CRP profile may underlie the increased vulnerability to anxiety- and depressive-like behaviors observed in these animals (Brocardo et al, 2012; Hellemans et al, 2008; 2010a,b; Raineki et al, 2016), consistent with the clinical literature indicating that individuals exposed to alcohol during gestation show increased vulnerability to mental health problems when compared to controls (Famy et al, 1998; O’Connor and Kasari, 2000; Pei et al, 2011). Moreover, it has been proposed that exposure to adversity and/or stress has a greater impact on individuals with PAE than on unexposed individuals, resulting in an even higher rate of mental health problems in that population (Hellemans et al, 2010a; McLachlan et al, 2016; Raineki et al, 2014).…”

Effects of physical exercise and social isolation on anxiety-related behaviors in two inbred rat strains

“…Increased locomotion may also lead to freezing behavior, increasing the time spent in the center in the OF (where the animal is place at the beginning of the test), thereby masking anxiolytic effects. Moreover, time spent in the center of the OF could be interpreted as an inappropriate behavioral response caused by previous stress (Raineki et al, 2016). The anxiolytic-like effect of voluntary PE was only evident in SHR rats.…”

Association between fetal sex and maternal plasma microRNA responses to prenatal alcohol exposure: evidence from a birth outcome-stratified cohort

“…Inherent transcriptomic differences between male and female fetal tissues like the placenta may further drive differences in the fetal response to alterations in the maternal environment, such as maternal exposure to stress (reviewed in [15]). Some studies in animal models and human populations have also documented sex differences in the pathophysiology of FASDs, and suggest that PAE-dependent sex differences can appear during the fetal period itself [42,49,51,64].…”