Premium
Effects of repeated prenatal glucocorticoid exposure on long‐term potentiation in the juvenile guinea‐pig hippocampus
Author(s) -
Setiawan Elaine,
Jackson Michael F.,
MacDonald John F.,
Matthews Stephen G.
Publication year - 2007
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2006.127381
Subject(s) - long term potentiation , endocrinology , medicine , glucocorticoid receptor , glucocorticoid , hippocampus , nmda receptor , hippocampal formation , offspring , biology , pregnancy , receptor , genetics
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 μ m ; 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 μ m cortisol depressed excitatory synaptic transmission in all treatment groups regardless of sex. Similarly, LTP was depressed by 10 μ m 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.