title: Prenatal corticosteroid exposure affects hippocampal plasticity and reduces lifespan.
abstract: 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.
authors.affiliation: Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, The Netherlands. c.w.noorlander-2@umcutrecht.nl
authors.forename: C W
authors.initials: CW
authors.lastname: Noorlander
authors.forename: G H A
authors.initials: GH
authors.lastname: Visser
authors.forename: G M J
authors.initials: GM
authors.lastname: Ramakers
authors.forename: P G J
authors.initials: PG
authors.lastname: Nikkels
authors.forename: P N E
authors.initials: PN
authors.lastname: de Graan
mesh_terms: D000305:Adrenal Cortex Hormones / Q000009:adverse effects*; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D018891:Dentate Gyrus / Q000187:drug effects / Q000503:physiopathology; D005260:Female; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology; D036881:Long-Term Synaptic Depression / Q000187:drug effects / Q000502:physiology; D008136:Longevity / Q000187:drug effects* / Q000502:physiology; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D008569:Memory Disorders / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009410:Nerve Degeneration / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology; D009473:Neuronal Plasticity / Q000187:drug effects* / Q000502:physiology; D009924:Organ Culture Techniques; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced* / Q000378:metabolism / Q000503:physiopathology; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors
chemical_list: D000305:Adrenal Cortex Hormones; D016194:Receptors, N-Methyl-D-Aspartate