PMID- 26506049 OWN - NLM STAT- MEDLINE DCOM- 20161213 LR - 20161230 IS - 1872-9711 (Electronic) IS - 0161-813X (Linking) VI - 52 DP - 2016 Jan TI - Cell proliferation and cell death are disturbed during prenatal and postnatal brain development after uranium exposure. PG - 34-45 LID - S0161-813X(15)30007-3 [pii] LID - 10.1016/j.neuro.2015.10.007 [doi] AB - The developing brain is more susceptible to neurotoxic compounds than adult brain. It is also well known that disturbances during brain development cause neurological disorders in adulthood. The brain is known to be a target organ of uranium (U) exposure and previous studies have noted that internal U contamination of adult rats induces behavioral disorders as well as affects neurochemistry and neurophysiological properties. In this study, we investigated whether depleted uranium (DU) exposure affects neurogenesis during prenatal and postnatal brain development. We examined the structural morphology of the brain, cell death and finally cell proliferation in animals exposed to DU during gestation and lactation compared to control animals. Our results showed that DU decreases cell death in the cortical neuroepithelium of gestational day (GD) 13 embryos exposed at 40mg/L and 120mg/L and of GD18 fetuses exposed at 120mg/L without modification of the number of apoptotic cells. Cell proliferation analysis showed an increase of BrdU labeling in the dentate neuroepithelium of fetuses from GD18 at 120mg/L. Postnatally, cell death is increased in the dentate gyrus of postnatal day (PND) 0 and PND5 exposed pups at 120mg/L and is associated with an increase of apoptotic cell number only at PND5. Finally, a decrease in dividing cells is observed in the dentate gyrus of PND21 rats developmentally exposed to 120mg/L DU, but not at PND0 and PND5. These results show that DU exposure during brain development causes opposite effects on cell proliferation and cell death processes between prenatal and postnatal development mainly at the highest dose. Although these modifications do not have a major impact in brain morphology, they could affect the next steps of neurogenesis and thus might disrupt the fine organization of the neuronal network. CI - Copyright (c) 2015 Elsevier Inc. All rights reserved. FAU - Legrand, M AU - Legrand M AD - Laboratoire de RadioToxicologie Experimentale, Service de Radiobiologie et d'Epidemiologie, Institut de Radioprotection et Surete Nucleaire, B.P. 17, 92262 Fontenay aux Roses Cedex, France. Electronic address: marie.legrand@irsn.fr. FAU - Elie, C AU - Elie C AD - Laboratoire de RadioToxicologie Experimentale, Service de Radiobiologie et d'Epidemiologie, Institut de Radioprotection et Surete Nucleaire, B.P. 17, 92262 Fontenay aux Roses Cedex, France. Electronic address: christelle.elie@irsn.fr. FAU - Stefani, J AU - Stefani J AD - Laboratoire de RadioToxicologie Experimentale, Service de Radiobiologie et d'Epidemiologie, Institut de Radioprotection et Surete Nucleaire, B.P. 17, 92262 Fontenay aux Roses Cedex, France. Electronic address: johanna.stefani@irsn.fr. FAU - N Flores AU - N Flores AD - Laboratoire de RadioToxicologie Experimentale, Service de Radiobiologie et d'Epidemiologie, Institut de Radioprotection et Surete Nucleaire, B.P. 17, 92262 Fontenay aux Roses Cedex, France. Electronic address: nicole.flores@irsn.fr. FAU - Culeux, C AU - Culeux C AD - Laboratoire de RadioToxicologie Experimentale, Service de Radiobiologie et d'Epidemiologie, Institut de Radioprotection et Surete Nucleaire, B.P. 17, 92262 Fontenay aux Roses Cedex, France. Electronic address: cecile.culeux@gmail.com. FAU - Delissen, O AU - Delissen O AD - Laboratoire de RadioToxicologie Experimentale, Service de Radiobiologie et d'Epidemiologie, Institut de Radioprotection et Surete Nucleaire, B.P. 17, 92262 Fontenay aux Roses Cedex, France. Electronic address: olivia.delissen@irsn.fr. FAU - Ibanez, C AU - Ibanez C AD - Laboratoire de RadioToxicologie Experimentale, Service de Radiobiologie et d'Epidemiologie, Institut de Radioprotection et Surete Nucleaire, B.P. 17, 92262 Fontenay aux Roses Cedex, France. Electronic address: chrystelle.ibanez@irsn.fr. FAU - Lestaevel, P AU - Lestaevel P AD - Laboratoire de RadioToxicologie Experimentale, Service de Radiobiologie et d'Epidemiologie, Institut de Radioprotection et Surete Nucleaire, B.P. 17, 92262 Fontenay aux Roses Cedex, France. Electronic address: philippe.lestaevel@irsn.fr. FAU - Eriksson, P AU - Eriksson P AD - Department of Environmental Toxicology, Uppsala University, Norbyvagen 18 A, 752 36 Uppsala, Sweden. Electronic address: per.eriksson@ebc.uu.se. FAU - Dinocourt, C AU - Dinocourt C AD - Laboratoire de RadioToxicologie Experimentale, Service de Radiobiologie et d'Epidemiologie, Institut de Radioprotection et Surete Nucleaire, B.P. 17, 92262 Fontenay aux Roses Cedex, France. Electronic address: celine.dinocourt@irsn.fr. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20151023 PL - Netherlands TA - Neurotoxicology JT - Neurotoxicology JID - 7905589 RN - 4OC371KSTK (Uranium) SB - IM MH - Animals MH - Animals, Newborn MH - Brain/*drug effects/*growth & development/pathology MH - Cell Death/*drug effects MH - Cell Proliferation/*drug effects MH - Cerebral Cortex/drug effects/pathology MH - Dentate Gyrus/drug effects/pathology MH - Dose-Response Relationship, Drug MH - Female MH - Hippocampus/drug effects/pathology MH - Male MH - Neurogenesis/drug effects MH - Pregnancy MH - Prenatal Exposure Delayed Effects/*pathology MH - Rats MH - Tissue Distribution MH - Uranium/pharmacokinetics/*toxicity OTO - NOTNLM OT - Brain development OT - Dentate gyrus OT - Heavy metal OT - Neurogenesis OT - Telencephalon EDAT- 2015/10/28 06:00 MHDA- 2016/12/15 06:00 CRDT- 2015/10/28 06:00 PHST- 2015/07/01 00:00 [received] PHST- 2015/10/13 00:00 [revised] PHST- 2015/10/13 00:00 [accepted] PHST- 2015/10/28 06:00 [entrez] PHST- 2015/10/28 06:00 [pubmed] PHST- 2016/12/15 06:00 [medline] AID - S0161-813X(15)30007-3 [pii] AID - 10.1016/j.neuro.2015.10.007 [doi] PST - ppublish SO - Neurotoxicology. 2016 Jan;52:34-45. doi: 10.1016/j.neuro.2015.10.007. Epub 2015 Oct 23.