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PMID: 17412773 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Effects of repeated prenatal glucocorticoid exposure on long-term potentiation in the juvenile guinea-pig hippocampus.

The Journal of physiology ·Vol. 581 ·No. Pt 3 ·2007-06-15 ·Pages 1033-42

Setiawan E, Jackson MF, MacDonald JF, Matthews SG

Abstract

Synthetic glucocorticoids (sGCs) are routinely used to treat women at risk of preterm labour to promote fetal lung maturation. There is now strong evidence that exposure to excess glucocorticoid during periods of rapid brain development has permanent consequences for endocrine function and behaviour in the offspring. Prenatal exposure to sGC alters the expression of N-methyl-D-aspartate receptor (NMDA-R) subunits in the fetal and neonatal hippocampus. Given the integral role of the NMDA-R in synaptic plasticity, we hypothesized that prenatal sGC exposure will have effects on hippocampal long-term potentiation (LTP) after birth. Further, this may occur in either the presence or absence of elevated cortisol concentrations, in vitro. Pregnant guinea-pigs were injected with betamethasone (Beta, 1 mg kg(-1)) or vehicle on gestational days (gd) 40, 41, 50, 51, 60 and 61 (term approximately 70 days), a regimen comparable to that given to pregnant women. On postnatal day 21, LTP was examined at Schaffer collateral synapses in the CA1 region of hippocampal slices prepared from juvenile animals exposed to betamethasone or vehicle, in utero. Subsequently, the acute glucocorticoid receptor (GR)- and mineralocorticoid receptor (MR)-dependent effects of cortisol (0.1-10 microM; bath applied 30 min before LTP induction) were examined. There was no effect of prenatal sGC treatment on LTP under basal conditions. The application of 10 microM cortisol depressed excitatory synaptic transmission in all treatment groups regardless of sex. Similarly, LTP was depressed by 10 microM cortisol in all groups, with the exception of Beta-exposed females, in which LTP was unaltered. Hippocampal MR and GR protein levels were increased in Beta-exposed females, but not in any other prenatal treatment group. This study reveals sex-specific effects of prenatal exposure to sGC on LTP in the presence of elevated cortisol, a situation that would occur in vivo during stress.

MeSH Terms
Animals Betamethasone/administration & dosage,pharmacology Birth Weight/drug effects Calcium-Calmodulin-Dependent Protein Kinase Type 2 Calcium-Calmodulin-Dependent Protein Kinases/metabolism Dose-Response Relationship, Drug Excitatory Postsynaptic Potentials/drug effects Female Gestational Age Glucocorticoids/administration & dosage,pharmacology Guinea Pigs Hippocampus/cytology,drug effects,growth & development,metabolism Hydrocortisone/blood,metabolism,pharmacology Hypothalamo-Hypophyseal System/drug effects,metabolism Injections, Subcutaneous Long-Term Potentiation/drug effects Male Neurons/drug effects,metabolism Phosphorylation Pituitary-Adrenal System/drug effects,metabolism Pregnancy Prenatal Exposure Delayed Effects Receptors, Glucocorticoid/drug effects,metabolism Receptors, Mineralocorticoid/drug effects,metabolism Receptors, N-Methyl-D-Aspartate/metabolism Sex Factors Time Factors
Chemicals
Glucocorticoids Receptors, Glucocorticoid Receptors, Mineralocorticoid Receptors, N-Methyl-D-Aspartate Betamethasone Calcium-Calmodulin-Dependent Protein Kinase Type 2 Calcium-Calmodulin-Dependent Protein Kinases Hydrocortisone
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Setiawan Elaine
Department of Physiology, Faculty of Medicine, University of Toronto, Medical Sciences Building, 1 King's College Circle, Toronto, Ontario M5S 1A8, Canada.
Jackson Michael F
MacDonald John F
Matthews Stephen G
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Article Info
Journal
The Journal of physiology
Abbr.
J Physiol
ISSN
0022-3751
DOI
10.1113/jphysiol.2006.127381
Published
2007-06-15
Epub
2007-00-05
Pages
1033-42
Language
English
Region
England
NLM ID
0266262
PMCID
PMC2170854
Subset
IM
External Links
PubMed source DOI: 10.1113/jphysiol.2006.127381 PMC Full Text View journal details
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