Prenatal glucocorticoid exposure affects learning and vulnerability of cholinergic neurons

Emgård, Mia; Paradisi, Mario Paglialunga; Pirondi, Stefania; Fernández, Mercedes; Giardino, Luciana; Calzà, Laura

doi:10.1016/j.neurobiolaging.2005.11.015

Cited by 24 publications

(12 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…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: 73%

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

et al. 2015

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 73%

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

et al. 2015

View full text Add to dashboard Cite

show abstract

“…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).…”

Section: Effects Of Prenatal Exogenous Glucocorticoidsmentioning

confidence: 97%

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

Grace

Kim

Rogers

2011

Birth Defects Research

View full text Add to dashboard Cite

Parental and environmental factors during the prenatal and postnatal periods permanently affect the physiology and metabolism of offspring, potentially increasing disease risk later in life. Underlying mechanisms are being elucidated, and effects on a number of organs and metabolic pathways are likely involved. In this review, we consider effects on the developing hypothalamic-pituitary-adrenal (HPA) axis, which may represent a common pathway for developmental programming. The focus is on prenatal and early postnatal development, during which the HPA axis may be programmed in a manner that affects health for a lifetime. Programming of the HPA axis involves, at least in part, epigenetic remodeling of chromatin, leading to alterations in the expression of genes in many organs and tissues involved in HPA activation and response, including the hippocampus and peripheral tissues.

show abstract

“…Rodents are more GC sensitive than primates and the teratogenic effects seen in rodent models are not directly applicable to the plausible effects in humans. Studies in rats have demonstrated a lower birth weight as well as a smaller number of pups after prenatal DEX exposure [43, 44]. Adult corticosteroid-exposed rodent offspring are further characterized by hypertension, hyperinsulinemia, hyperglycemia, hyperactivity of the HPA axis, and altered affective behavior, reminiscent of anxiety.…”

Section: Reasons For Concernmentioning

confidence: 99%

Prenatal Treatment of Congenital Adrenal Hyperplasia: Long-Term Effects of Excess Glucocorticoid Exposure

2018

View full text Add to dashboard Cite

Prenatal treatment of congenital adrenal hyperplasia with dexamethasone (DEX) has been in use since the mid-1980s and has proven effective at reducing virilization of external genitalia in affected girls. However, multiple experimental studies on animals and clinical studies on humans show that prenatal administration of glucocorticoids may cause unwanted adverse effects which have raised concerns about the long-term safety of the treatment. The long-term outcome of prenatal DEX treatment on cognition has been investigated, but the results are still conflicting. Overall, most of the evidence points towards a negative effect on executive functions where girls seem to be more susceptible than boys. Some effects on social behavior have been observed, but results are still contradictory and treated children are mostly well adapted. Cardiovascular, renal, and metabolic function are still areas to be investigated. Larger studies are warranted to investigate areas other than cognition and behavior and to be able to draw more definitive conclusions about prenatal DEX treatment.

show abstract

Prenatal glucocorticoid exposure affects learning and vulnerability of cholinergic neurons

Cited by 24 publications

References 52 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

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

Prenatal Treatment of Congenital Adrenal Hyperplasia: Long-Term Effects of Excess Glucocorticoid Exposure

Contact Info

Product

Resources

About