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Prenatal corticosteroid exposure affects hippocampal plasticity and reduces lifespan
Author(s) -
Noorlander C.W.,
Visser G.H.A.,
Ramakers G.M.J.,
Nikkels P.G.J.,
de Graan P.N.E.
Publication year - 2007
Publication title -
developmental neurobiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.716
H-Index - 129
eISSN - 1932-846X
pISSN - 1932-8451
DOI - 10.1002/dneu.20583
Subject(s) - hippocampal formation , dentate gyrus , dexamethasone , hippocampus , endocrinology , offspring , long term potentiation , glucocorticoid , medicine , synaptic plasticity , biology , morris water navigation task , corticosteroid , neuroscience , pregnancy , receptor , genetics
Synthetic corticosteroids, such as dexamethasone, are frequently administered to pregnant women at risk for preterm delivery. Endogenous corticosteroids are essential for normal development, but exposure to therapeutic doses at critical developmental stages may have adverse effects on the central nervous system. Major concern has arisen about long‐term effects of corticosteroid treatment on brain plasticity, particularly in the hippocampus. Therefore, we analyzed the molecular, cellular, and behavioral effects of prenatal dexamethasone treatment on the adult hippocampus. Pregnant mice were treated at embryonic day 15.5 with a single dose of dexamethasone or saline. Adult offspring was analyzed for hippocampal neuron loss, cell proliferation, and NMDA receptor subunit expression. Hippocampal function was assessed in the Morris water maze and synaptic plasticity in the CA1 field by determining frequency dependence of LTP and LTD in hippocampal slices. Prenatal dexamethasone treatment decreased hippocampal cell proliferation in the dentate gyrus. Treated mice showed reduced LTD, impaired spatial learning, and a marked reduction in lifespan. Our data show long‐term adverse effects of prenatal dexamethasone treatment on hippocampal function in mice and suggest accelerated aging. These findings indicate that it is important to be restrictive with corticosteroid administration during fetal development because of the lifelong consequences. © 2007 Wiley Periodicals, Inc. Develop Neurobiol, 2008