Prenatal stress reduces postnatal neurogenesis in rats selectively bred for high, but not low, anxiety: possible key role of placental 11β‐hydroxysteroid dehydrogenase type 2

Abstract

Prenatal stress (PS) produces persistent abnormalities in anxiety-related behaviors, stress responsivity, susceptibility to psychopathology and hippocampal changes in adult offspring. The hippocampus shows a remarkable degree of structural plasticity, notably in response to stress and glucocorticoids. We hypothesized that PS would differentially affect hippocampal neurogenesis in rats selectively bred for genetic differences in anxiety-related behaviors and stress responsivity. Pregnant dams of high anxiety-related behavior (HAB) and low anxiety-related behavior (LAB) strains were stressed between days 5 and 20 of pregnancy. The survival of newly generated hippocampal cells was found to be significantly lower in 43-day-old HAB than in LAB male offspring of unstressed pregnancies. PS further reduced newly generated cell numbers only in HAB rats, and this was paralleled by a reduction in doublecortin-positive cell numbers, indicative of reduced neurogenesis. As maternal plasma corticosterone levels during PS were similar in both strains, we examined placental 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2), which catalyses rapid inactivation of maternal corticosterone to inert 11-dehydrocorticosterone and thus serves as a physiological 'barrier' to maternal glucocorticoids. PS significantly increased placental 11beta-HSD2 activity in LAB, but not HAB, rats. We conclude that PS differentially affects the number of surviving newly generated cells and neurogenesis in HAB and LAB rats. The high sensitivity of hippocampal neurogenesis to PS in HAB rats is paralleled by a failure to increase placental 11beta-HSD2 activity after stress rather than by different maternal corticosterone responses. Hence, stress-induced placental 11beta-HSD2 expression may be critical in protecting the fetal brain from maternal stress-induced effects on adult neurogenesis.

Chronic agomelatine treatment corrects behavioral, cellular, and biochemical abnormalities induced by prenatal stress in rats

“…It is a general belief that hippocampal neurogenesis is enhanced by antidepressant drugs (Santarelli et al 2003; reviewed by Malberg and Schechter 2005;Tanti and Belzung 2010). However, there are exceptions (Marlatt et al 2010) and, in addition, the action of antidepressants on neurogenesis might be critically influenced by age, gender, and stress context (Oitzl et al 2000;Navailles et al 2008;Lucassen et al 2009;2010a;Oomen et al 2009Oomen et al , 2010. In a mouse model of depression induced by chronic corticosterone treatment, only some "therapeutic effects" of fluoxetine are neurogenesisdependent (David et al 2009), and there is also evidence that antidepressants retain their "therapeutic" efficacy when neurogenesis is blocked by a cytostatic drug (Bessa et al 2009).…”

Electrophysiological insights into the enduring effects of early life stress on the brain

“…A variety of different hormonal and environmental exposures regulate the genesis of new cells, which ultimately may also influence the electrophysiological characteristics of the target circuits. Early life stress exposures, either prenatal (Coe et al 2003;Lemaire et al 2000;Lucassen et al 2009;Mandyam et al 2008) or postnatal (Lemaire et al 2006;Mirescu et al 2004), have been shown consistently to reduce neurogenesis in the adult dentate gyrus in rodents and non-human primates, an effect which may be mediated via corticosterone (Mirescu et al 2004). The consequences of reduced neurogenesis in the dentate gyrus on the electrophysiological properties of this structure, and those it connects to, may be related to the observed effects of early life stress on such outcomes as hippocampal LTP and LTD, as described earlier.…”

Regulation of Adult Neurogenesis and Plasticity by (Early) Stress, Glucocorticoids, and Inflammation

“…Rodent studies over the past decades have shown that neurogenesis appears to be very sensitive to stress, particularly when stress occurs during the perinatal period (Korosi et al 2012). Also, perinatal stress can induce reductions in AN in the offspring (Lemaire et al 2000;Coe et al 2003;Lucassen et al 2009) (although exceptions have been reported [Tauber et al 2008]). Such reductions may, in part, occur through epigenetic modifications, often in a sex-dependent manner (Lucassen et al 2013b).…”