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This Article Full Text Full Text (PDF) All Versions of this Article: 581/3/1033    most recent jphysiol.2006.127381v1 Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Setiawan, E. Articles by Matthews, S. G. Search for Related Content PubMed PubMed Citation Articles by Setiawan, E. Articles by Matthews, S. G. Related Collections Neuroscience

Departments of
¹ Physiology
² Obstetrics and Gynecology
³ Medicine, Faculty of Medicine, University of Toronto, Medical Sciences Building, 1 King's College Circle, Toronto, Ontario M5S 1A8, Canada

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 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 µM; 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 µM cortisol depressed excitatory synaptic transmission in all treatment groups regardless of sex. Similarly, LTP was depressed by 10 µM 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.

(Received 22 December 2006; accepted after revision 30 March 2007; first published online 5 April 2007)
Corresponding author S. G. Matthews: Department of Physiology, Faculty of Medicine, University of Toronto, Medical Sciences Building, 1 King's College Circle, Toronto, Ontario M5S 1A8, Canada. Email: stephen.matthews{at}utoronto.ca