Gender-Dependent Effects of Early Maternal Separation and Variable Chronic Stress on Vasopressinergic Activity and Glucocorticoid Receptor Expression in Adult Rats

Abstract

The aim of the present study was to investigate the influence of early maternal separation on Fos, arginine vasopressin (AVP) and glucocorticoid receptor (GR) expression in the medial parvocellular portion of the paraventricular hypothalamic nucleus (PaMP), and GR expression in the hippocampus of adult male and female rats subjected to variable chronic stress (VCS). Male and female Wistar rats were isolated 4.5 h daily, during the first 3 weeks of life. At 48 days of age, the rats were exposed to VCS. Nonmaternally separated (NMS) females had a higher number of activated AVP neurons than NMS male rats. Maternally separated (MS) females subjected to VCS also showed a higher number of Fos/AVP double-labeled neurons than males with the same treatment. Males and females subjected to early maternal separation and VCS, compared with the MS animals, showed a decrease in the expression of GR in the PaMP. As regards GR expression in the hippocampus, MS animals subjected to VCS as adults, both males and females, showed an increase in GR expression in the subfields CA1, CA2 and CA3. The increase in AVP-immunoreactive neurons coexpressing Fos in response to stress in females exposed to early maternal separation suggests that perhaps early life stress results in a more reactive neuroendocrine stress response in females. Furthermore, our results demonstrate that the different anatomical levels of the hypothalamic-pituitary-adrenal axis have different roles related to its stress response and support the evidence of regional specificity in GR regulation.

Effect of maternal separation and chronic stress on hippocampal-dependent memory in young adult rats: evidence for the match-mismatch hypothesis

“…In these animals, lower levels of ACTH and plasmatic corticosterone were detected compared with NMS-CVS (Renard et al, 2007). They also showed a greater number of GR immunoreactive cells in CA areas compared to controls (Renard et al, 2010).…”

Modulation of the Hypothalamic-Pituitary-Adrenal Axis by Early Life Stress Exposure

“…While MS seems to result in significantly higher corticosterone stress responses in adulthood (Ladd et al, 2004, 2005; Plotsky et al, 2005; Lippmann et al, 2007; Lajud et al, 2012), the additional experience of chronic stress in adult life has been shown to normalize these responses to the level observed in non-stressed non-MS controls (Ladd et al, 2005) or to even reduce basal ACTH and corticosterone levels compared to stressed non-MS animals (Renard et al, 2007). These effects were associated with an upregulation in hippocampal GR expression, and a normalization of GR levels in the PVN (Renard et al, 2010). Moreover, exposure to chronic stress reduced amygdala CRH mRNA expression in MS offspring and did not induce an increase in PVN expression levels (as observed in the stressed control animals; Ladd et al, 2005).…”

Maternal separation as a model of brain–gut axis dysfunction

“…Many studies have indicated pronounced sex-dependent differences of MS-induced effects (Barna et al 2003;Oreland et al 2009;Renard et al 2010;Rosztoczy et al 2003). This is of particular relevance to IBS where significantly more GI, psychological and somatic symptoms are associated with the female gender (Cain et al 2009).…”