Prenatal Dexamethasone Impairs Behavior and the Activation of the BDNF Exon IV Promoter in the Paraventricular Nucleus in Adult Offspring

Abstract

Prenatal manipulations to the hypothalamic-pituitary-adrenal axis are shown to affect auditory responses to an acoustic challenge as well as behavior in adult life. To achieve these results, we examined the effect of prenatal dexamethasone (DEX) treatment in male and female adult rat offspring by assessing body and adrenal weight, anxiety using the elevated plus maze (EPM), and acoustic startle responses as well as the effects of acoustic challenge in the paraventricular nucleus (PVN). DEX male offspring had reduced adrenal gland weight in adult life and demonstrated anxiolytic-like behavior when tested on the EPM. The acoustic startle amplitude in naive DEX-treated male offspring was significantly higher compared with saline (SAL)-treated males and females and DEX-treated females. When challenged with either a glucocorticoid agonist or antagonist, the startle response of the SAL-treated males and females significantly increased or decreased in the presence of agonist and antagonist treatment, respectively, whereas DEX males and females were not affected. Acoustic challenge caused an increase in c-fos mRNA and glucocorticoid receptor nuclear translocation in the PVN of all groups. BDNF and TrkB mRNA increased in the PVN after acoustic challenge in the SAL-treated males and females but not in the DEX males or females. These findings exemplify the differential sensitivity of the developing nervous and endocrine systems to prenatal hormonal stress and demonstrate that prenatal DEX treatment elicits long-term behavioral alterations related to anxiety and auditory processing.

Maternal influences on epigenetic programming of the developing hypothalamic‐pituitary‐adrenal axis

“…DEX administration in rats reduced social play in juvenile offspring, reduced acoustic startle reflex, increased acoustic startle prepulse inhibition, and increased locomotor activity after amphetamine challenge (Kleinhaus et al, 2010). Spatial learning deficits (Emgard et al, 2007) and anxiolytic behavior (Hossain et al, 2008) are observed in DEX-treated males during adulthood. CORT exposure in mice during the last week of gestation and throughout weaning also caused increased locomotor activity in the open field and depressive-like effects in the Porsolt swim test (Pechnick et al, 2006).…”

Protective effects of maternal nutritional supplementation with lactoferrin on growth and brain metabolism

“…exposure to dexamethasone was reported to decrease the level of BDNF mRNA in the rat hippocampus (26), and prenatal dexamethasone exposure blocks the stimulated BDNF elevation in the paraventricular nucleus (27). In the same way, in vitro, dexamethasone prevents activity-dependent increases in BDNF in rat hippocampal neurons (28) through different mechanisms including (i) inhibition of postsynaptic Ca( 2+ ) influx (29), (ii) inhibition of presynaptic glutamate release (29) via a direct glucocorticoid receptor-BDNF receptor interaction (30), and (iii) blockade of the signaling pathway mediating the BDNF-induced synaptic proteins involved in neuron maturation (29).…”

Reduced Mobility But Unaffected Startle Response in Female Rats Exposed to Prenatal Dexamethasone: Different Sides to a Phenotype

“…Data from animal studies provide evidence that prenatal exposure to glucocorticoids restricts fetal growth and suggest a role in programming the individual to adult disease [Hossain et al, 2008;Nagano et al, 2008;Newnham and Moss, 2001;Seckl, 2004;Seckl and Meaney, 2004;Weaver, 2009].…”