Induction of a Hyperanxious State by Antenatal Dexamethasone: A Case for Less Detrimental Natural Corticosteroids

Oliveira, Miguel; Bessa, João M.; Mesquita, Ana; Tavares, Hugo Miguel Braga Almeida; Carvalho, André Filipe Couto; Silva, Rui; Pêgo, José M.; Cerqueira, João José; Palha, Joana Almeida; Almeida, Osborne F. X.; Sousa, Nuno

doi:10.1016/j.biopsych.2005.08.020

Cited by 62 publications

(83 citation statements)

References 55 publications

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“…Despite many published studies on the association between prenatal glucocorticoid exposure and reduced cognitive performance in male animals [33,34,35,36], we and others have failed to observe deficits in learning ability and memory in the offspring of rats born to mothers that were either stressed or exposed to exogenous corticosteroids during pregnancy [37,38]. …”

Section: Discussionmentioning

confidence: 99%

Effects of Melatonin on Prenatal Dexamethasone-Induced Epigenetic Alterations in Hippocampal Morphology and Reelin and Glutamic Acid Decarboxylase 67 Levels

et al. 2015

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Prenatal glucocorticoid exposure causes brain damage in adult offspring; however, the underlying mechanisms remain unclear. Melatonin has been shown to have beneficial effects in compromised pregnancies. Pregnant Sprague-Dawley rats were administered vehicle (VEH) or dexamethasone between gestation days 14 and 21. The programming effects of prenatal dexamethasone exposure on the brain were assessed at postnatal days (PND) 7, 42, and ∼120. Melatonin was administered from PND21 to the rats exposed to dexamethasone, and the outcome was assessed at ∼PND120. In total, there were four groups: VEH, vehicle plus melatonin (VEHM), prenatal dexamethasone-exposure (DEX), and prenatal dexamethasone exposure plus melatonin (DEXM). Spatial memory, gross hippocampal morphology, and hippocampal biochemistry were examined. Spatial memory assessed by the Morris water maze showed no significant differences among the four groups. Brain magnetic resonance imaging showed that all rats with prenatal dexamethasone exposure (DEX + DEXM) exhibited increased T2-weighted signals in the hippocampus. There were no significant differences in the levels of mRNA expression of hippocampal reln, which encodes reelin, and GAD1, which encodes glutamic acid decarboxylase 67, at PND7. At both PND42 and ∼PND120, reln and GAD1 mRNA expression levels were decreased. At ∼PND120, melatonin restored the reduced levels of hippocampal reln and GAD1 mRNA expression in the DEXM group. In addition, melatonin restored the reln mRNA expression levels by (1) reducing DNA methyltransferase 1 (DNMT1) mRNA expression and (2) reducing the binding of DNMT1 and the methyl-CpG binding protein 2 (MeCP2) to the reln promoter. The present study showed that prenatal dexamethasone exposure induced gross alterations in hippocampal morphology and reduced the levels of hippocampal mRNA expression of reln and GAD1. Spatial memory was unimpaired. Thus, melatonin had a beneficial effect in restoring hippocampal reln mRNA expression by reducing DNMT1 and MeCP2 binding to the reln promoter.

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Section: Discussionmentioning

confidence: 99%

Effects of Melatonin on Prenatal Dexamethasone-Induced Epigenetic Alterations in Hippocampal Morphology and Reelin and Glutamic Acid Decarboxylase 67 Levels

et al. 2015

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“…This hypothesis is based on the observation that antenatal DEX administration leads to an impaired resilience to stressors in adulthood. 22 Interestingly, O'Regan et al 7 demonstrated that prenatal DEX treatment in rats in the last week of pregnancy results in lower basal BP values of Ϸ4 to 8 mm Hg, whereas even mild disturbances or a more severe stressor lead to increased BP values Յ30 mm Hg higher than controls. Thereby, they used a radiotelemetry method to monitor BP that is unaffected by stress artifacts of measurement.…”

Section: Discussionmentioning

confidence: 99%

Prenatal Dexamethasone Exposure Does Not Alter Blood Pressure and Nephron Number in the Young Adult Marmoset Monkey

et al. 2009

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Abstract-The influence of prenatal factors on the development of arterial hypertension has gained considerable interest in recent years. Prenatal dexamethasone exposure was found to induce hypertension and to alter nephron number and size in rodents and sheep. However, it is not clear whether these findings are applicable to nonhuman primates. Thus, we examined the effects of prenatal dexamethasone treatment on blood pressure (BP) and nephron number in marmoset monkeys. Fifty-two marmosets were allotted to 3 groups according to the gestational stage during which their mothers were exposed to oral 5-mg/kg dexamethasone for 7 days (gestation period: 20 weeks): (1) the early dexamethasone group at week 7; (2) the late dexamethasone group at week 13; and (3) the control group. BP was determined by telemetric (nϭ12) or cuff measurements (nϭ30), along with cystatin C, proteinuria, and body weight. All of the animals were euthanized at the age of 24 months, and glomerular number and volume were determined. Prenatal exposure to dexamethasone did not lead to a significant difference between the groups with regard to BP, kidney morphology and function, or body weight. BP correlated significantly with body weight, relative kidney weight, and mean glomerular volume and the body weight with the glomerular volume regardless of dexamethasone treatment. In conclusion, prenatal exposure to dexamethasone in marmosets does not, in contrast to other mammals studied, result in hypertension or changes in kidney morphology. Our data support the role of body weight as a predictor of elevated glomerular volume and BP development rather than prenatal dexamethasone exposure. Key Words: hypertension Ⅲ dexamethasone Ⅲ prenatal programming Ⅲ marmoset monkeys Ⅲ glomeruli number S ynthetic glucocorticoids such as dexamethasone (DEX) are often given to pregnant women with expected preterm birth to accelerate fetal pulmonary maturation and to prevent respiratory distress syndrome. However, prenatal administration of DEX may induce hypertension in combination with a lower number and increased volume of glomeruli in the later life of the offspring, as has been demonstrated for rodents and sheep. 1 The fetal origin of chronic diseases in adulthood was first proposed by Barker et al ("Barker hypothesis"). 2 The original epidemiological studies linked low birth weight with the risk of fatal ischemic heart disease 2 and with an increased risk for metabolic syndrome, including hypertension, dyslipidemia, and type 2 diabetes mellitus. 3 Therefore, the prevalence of metabolic syndrome, including hypertension, increased progressively, in both men and women, from those who had the highest to those who had the lowest birth weights. 3 Several subsequent experimental studies in rats and sheep inducing intrauterine growth restriction by maternal glucocorticoid exposure confirmed these epidemiological data. 1 A decreased number of glomeruli in the kidney were, therefore, proposed as one possible pathogenetic mechanism for the induction of hypertension. 3,4 The ...

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“…We previously demonstrated that fetal exposure to GC leads to hyper-emotionality in adulthood (11). In addition, we showed that prenatal DEX/GC targets the mesolimbic dopaminergic system (12); this system comprises projections from the ventral tegmental area (VTA) to the nucleus accumbens (NAcc) and is strongly implicated in motivational and reward aspects of addictive behaviors (13)(14)(15).…”

Section: Introductionmentioning

confidence: 99%

Mechanisms of initiation and reversal of drug-seeking behavior induced by prenatal exposure to glucocorticoids

et al. 2011

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Induction of a Hyperanxious State by Antenatal Dexamethasone: A Case for Less Detrimental Natural Corticosteroids

Cited by 62 publications

References 55 publications

Effects of Melatonin on Prenatal Dexamethasone-Induced Epigenetic Alterations in Hippocampal Morphology and Reelin and Glutamic Acid Decarboxylase 67 Levels

Effects of Melatonin on Prenatal Dexamethasone-Induced Epigenetic Alterations in Hippocampal Morphology and Reelin and Glutamic Acid Decarboxylase 67 Levels

Prenatal Dexamethasone Exposure Does Not Alter Blood Pressure and Nephron Number in the Young Adult Marmoset Monkey

Mechanisms of initiation and reversal of drug-seeking behavior induced by prenatal exposure to glucocorticoids

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