Prenatal corticosteroid exposure affects hippocampal plasticity and reduces lifespan

• Published in: Developmental neurobiology (Hoboken, N.J.) Vol. 68; no. 2; pp. 237 - 246
• Main Authors: Noorlander, C.W., Visser, G.H.A., Ramakers, G.M.J., Nikkels, P.G.J., de Graan, P.N.E.
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01-02-2008
• Subjects: Adrenal Cortex Hormones - adverse effects; aging; Animals; Cell Proliferation - drug effects; Dentate Gyrus - drug effects; Dentate Gyrus - physiopathology; dexamethasone; Female; glucocorticoids; hippocampus; Hippocampus - drug effects; Hippocampus - metabolism; Hippocampus - physiopathology; Long-Term Potentiation - drug effects; Long-Term Potentiation - physiology; Long-Term Synaptic Depression - drug effects; Long-Term Synaptic Depression - physiology; Longevity - drug effects; Longevity - physiology; Male; Maze Learning - drug effects; Maze Learning - physiology; Memory Disorders - chemically induced; Memory Disorders - metabolism; Memory Disorders - physiopathology; Mice; Mice, Inbred C57BL; Nerve Degeneration - chemically induced; Nerve Degeneration - metabolism; Nerve Degeneration - physiopathology; Neuronal Plasticity - drug effects; Neuronal Plasticity - physiology; Organ Culture Techniques; Pregnancy; Prenatal Exposure Delayed Effects - chemically induced; Prenatal Exposure Delayed Effects - metabolism; Prenatal Exposure Delayed Effects - physiopathology; proliferation; Receptors, N-Methyl-D-Aspartate - drug effects; Receptors, N-Methyl-D-Aspartate - metabolism; Time Factors
• ISSN: 1932-8451; 1932-846X
• DOI: 10.1002/dneu.20583

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