Impact of adolescent stress on the expression of stress‐related receptors in the hippocampus of animals exposed to alcohol prenatally

Abstract

Many functions of the hippocampus are affected by prenatal alcohol exposure (PAE). In particular, dysregulation of the stress response is especially important because individuals with PAE carry increased risks for exposure to stressful environments throughout life. Little is known, though, about how adolescent stress in the context of PAE-related stress system dysregulation may further alter hippocampal development. Here, we investigate the short- and long-term effects of adolescent chronic mild stress (CMS) on mRNA expression of stress-related mineralocorticoid (MR), glucocorticoid (GR), and type 1 CRH (CRHR1) receptors in the dorsal and ventral hippocampal formation of PAE and control rats. Our results indicate that PAE affects the expression of stress-related receptors in the hippocampus; however, PAE effects were more prominent during adolescence, as MR and CRHR1 mRNA expression were altered in both male and female PAE animals, with GR mRNA expression alterations observed only in PAE female. In adulthood, the effects of PAE were restricted to alterations in CRHR1 mRNA expression in females, while there were no effects in males. In contrast, the effects of adolescent CMS were more pronounced in adulthood, long after stress exposure termination. Importantly, PAE animals were less responsive to adolescent CMS, with effects only on CRHR1 in PAE animals compared to the altered MR, GR, and CRHR1 mRNA expression observed in controls. Together, our results show that PAE and adolescent CMS induce dynamic alterations in the expression of stress-related receptors in the hippocampal formation that manifest differently depending on the age and sex of the animal.

Interactive effects of prenatal alcohol exposure and chronic stress in adulthood on anxiety-like behavior and central stress-related receptor mRNA expression: Sex- and time-dependent effects

“…PAE-induced dysregulation of these key receptor systems may predispose individuals to the adverse effects of stress over the life course and increase vulnerability to stress-related disorders such as depression and anxiety. In support of this, we have found that chronic stress during adolescence may further alter mRNA expression of these stress-related receptors and anxiety-like behavior in PAE compared to C animals, and may do so in a sex-dependent manner (Raineki et al, 2018, 2016). As well, we recently showed that PAE and chronic stress in adulthood interact to result in sexually-dimorphic and time-dependent dysregulation of the neurocircuitry underlying behavioral, emotional and stress regulation, as well as alterations in depressive-like (forced swim test) behavior (Lam et al, 2018).…”

“…CRHR1 mRNA and protein expression are also decreased in the hippocampus of adolescent PAE males (Caldwell et al, 2015; Raineki et al, 2018). Additionally, PAE decreases MR mRNA expression in the adult female hippocampus (Sliwowska et al, 2008; Uban et al, 2013), and alters hippocampal MR mRNA expression in adolescent male and GR mRNA expression in adolescent female rats (Raineki et al, 2018). PAE-induced dysregulation of these key receptor systems may predispose individuals to the adverse effects of stress over the life course and increase vulnerability to stress-related disorders such as depression and anxiety.…”

“…We and others have shown previously that PAE has widespread effects on these stress-related receptors in the brain. Specifically, PAE increases CRH mRNA expression in the central nucleus of the amygdala in adult males and females (Lan et al, 2015), and differentially decreases CRHR1 mRNA expression in the mPFC, amygdala, hippocampus, and pituitary of adult males and females (Glavas et al, 2007; Raineki et al, 2018, 2016). CRHR1 mRNA and protein expression are also decreased in the hippocampus of adolescent PAE males (Caldwell et al, 2015; Raineki et al, 2018).…”

“…Specifically, PAE increases CRH mRNA expression in the central nucleus of the amygdala in adult males and females (Lan et al, 2015), and differentially decreases CRHR1 mRNA expression in the mPFC, amygdala, hippocampus, and pituitary of adult males and females (Glavas et al, 2007; Raineki et al, 2018, 2016). CRHR1 mRNA and protein expression are also decreased in the hippocampus of adolescent PAE males (Caldwell et al, 2015; Raineki et al, 2018). Additionally, PAE decreases MR mRNA expression in the adult female hippocampus (Sliwowska et al, 2008; Uban et al, 2013), and alters hippocampal MR mRNA expression in adolescent male and GR mRNA expression in adolescent female rats (Raineki et al, 2018).…”

Detection of Prenatal Alcohol Exposure Using Machine Learning Classification of Resting-State Functional Network Connectivity Data

“…In fact, studies conducted in rats and voles have revealed modest contributions of stress in normal and awake animals after an acclimation procedure (Liang, King, & Zhang, 2011, 2012; Reed, Pira, & Febo, 2013; Yee et al, 2016). However, changes in the sensitivity of stress-related circuitry including the hippocampus and the hypothalamic-pituitary-adrenal (HPA) axis following PAE are well documented (Hellemans, Verma, Yoon, Yu, & Weinberg, 2008; Lam, Raineki, Ellis, Yu, & Weinberg, 2018; Raineki, Ellis, & Weinberg, 2018), and carry the potential to introduce a different set of confounds in an awake scanning procedure. Next, animals in this investigation reached adulthood by the time image acquisition was conducted.…”