Prenatal Restraint Stress Generates Two Distinct Behavioral and Neurochemical Profiles in Male and Female Rats

Abstract

Prenatal Restraint Stress (PRS) in rats is a validated model of early stress resulting in permanent behavioral and neurobiological outcomes. Although sexual dimorphism in the effects of PRS has been hypothesized for more than 30 years, few studies in this long period have directly addressed the issue. Our group has uncovered a pronounced gender difference in the effects of PRS (stress delivered to the mothers 3 times per day during the last 10 days of pregnancy) on anxiety, spatial learning, and a series of neurobiological parameters classically associated with hippocampus-dependent behaviors. Adult male rats subjected to PRS (“PRS rats”) showed increased anxiety-like behavior in the elevated plus maze (EPM), a reduction in the survival of newborn cells in the dentate gyrus, a reduction in the activity of mGlu1/5 metabotropic glutamate receptors in the ventral hippocampus, and an increase in the levels of brain-derived neurotrophic factor (BDNF) and pro-BDNF in the hippocampus. In contrast, female PRS rats displayed reduced anxiety in the EPM, improved learning in the Morris water maze, an increase in the activity of mGlu1/5 receptors in the ventral and dorsal hippocampus, and no changes in hippocampal neurogenesis or BDNF levels. The direction of the changes in neurogenesis, BDNF levels and mGlu receptor function in PRS animals was not consistent with the behavioral changes, suggesting that PRS perturbs the interdependency of these particular parameters and their relation to hippocampus-dependent behavior. Our data suggest that the epigenetic changes in hippocampal neuroplasticity induced by early environmental challenges are critically sex-dependent and that the behavioral outcome may diverge in males and females.

Effects of maternal exposure to social stress during pregnancy: consequences for mother and offspring

“…By contrast, prenatal social stress in late pregnancy does not appear to affect anxiety-type behaviour in female offspring (Brunton & Russell 2010), except when given in combination with another psychological stressor (restraint) in early-mid pregnancy (Bosch et al 2007). Other studies using different prenatal stress models in rats have also reported sex differences (Zagron & Weinstock 2006, Mueller & Bale 2008, including reduced anxiety in Effects of social stress during pregnancy R179 prenatally stressed females compared with males (Zuena et al 2008).…”

Epigenetics and developmental programming of welfare and production traits in farm animals

“…spatial tasks; Darnaudery and Maccari 2008). Many studies report sexdependent effects, with males typically showing an increase in anxiety after prenatal stress and dysmasculinised behaviours, whereas females show converse behavioural responses (Zuena et al 2008). The release of glucocorticoids by the stressed mother, which can cross the placenta to affect the developing offspring, appears to mediate these responses (Mesquita et al 2009;Harris and Seckl 2011) and changes to over 700 genes in the fetus, in a region-and sex-specific manner, have been reported (Mychasiuk et al 2011).…”

Adult Neurogenesis and Mental Illness

“…Prenatal stress produces long-lasting deficits in the production and survival of new neurons into adulthood (Koo et al, 2003;Lemaire et al, 2000;Zuena et al, 2008). A recent study indicates that infection during pregnancy reduces cell proliferation and neurogenesis in both juvenile and adult offspring (Lin and Wang, 2014).…”