Cell proliferation and cell death are disturbed during prenatal and postnatal brain development after uranium exposure.
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.
Laboratoire de RadioToxicologie Expérimentale, Service de Radiobiologie et d'Epidémiologie, Institut de Radioprotection et Sûreté Nucléaire, B.P. 17, 92262 Fontenay aux Roses Cedex, France. Electronic address: marie.legrand@irsn.fr.
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Legrand
Laboratoire de RadioToxicologie Expérimentale, Service de Radiobiologie et d'Epidémiologie, Institut de Radioprotection et Sûreté Nucléaire, B.P. 17, 92262 Fontenay aux Roses Cedex, France. Electronic address: christelle.elie@irsn.fr.
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Elie
Laboratoire de RadioToxicologie Expérimentale, Service de Radiobiologie et d'Epidémiologie, Institut de Radioprotection et Sûreté Nucléaire, B.P. 17, 92262 Fontenay aux Roses Cedex, France. Electronic address: johanna.stefani@irsn.fr.
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Stefani
Laboratoire de RadioToxicologie Expérimentale, Service de Radiobiologie et d'Epidémiologie, Institut de Radioprotection et Sûreté Nucléaire, B.P. 17, 92262 Fontenay aux Roses Cedex, France. Electronic address: nicole.flores@irsn.fr.
N Florès
Laboratoire de RadioToxicologie Expérimentale, Service de Radiobiologie et d'Epidémiologie, Institut de Radioprotection et Sûreté Nucléaire, B.P. 17, 92262 Fontenay aux Roses Cedex, France. Electronic address: cecile.culeux@gmail.com.
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Culeux
Laboratoire de RadioToxicologie Expérimentale, Service de Radiobiologie et d'Epidémiologie, Institut de Radioprotection et Sûreté Nucléaire, B.P. 17, 92262 Fontenay aux Roses Cedex, France. Electronic address: olivia.delissen@irsn.fr.
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Delissen
Laboratoire de RadioToxicologie Expérimentale, Service de Radiobiologie et d'Epidémiologie, Institut de Radioprotection et Sûreté Nucléaire, B.P. 17, 92262 Fontenay aux Roses Cedex, France. Electronic address: chrystelle.ibanez@irsn.fr.
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Ibanez
Laboratoire de RadioToxicologie Expérimentale, Service de Radiobiologie et d'Epidémiologie, Institut de Radioprotection et Sûreté Nucléaire, B.P. 17, 92262 Fontenay aux Roses Cedex, France. Electronic address: philippe.lestaevel@irsn.fr.
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Lestaevel
Department of Environmental Toxicology, Uppsala University, Norbyvägen 18 A, 752 36 Uppsala, Sweden. Electronic address: per.eriksson@ebc.uu.se.
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Eriksson
Laboratoire de RadioToxicologie Expérimentale, Service de Radiobiologie et d'Epidémiologie, Institut de Radioprotection et Sûreté Nucléaire, B.P. 17, 92262 Fontenay aux Roses Cedex, France. Electronic address: celine.dinocourt@irsn.fr.
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Dinocourt
D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000187:drug effects* / Q000254:growth & development* / Q000473:pathology; D016923:Cell Death / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D002540:Cerebral Cortex / Q000187:drug effects / Q000473:pathology; D018891:Dentate Gyrus / Q000187:drug effects / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology; D008297:Male; D055495:Neurogenesis / Q000187:drug effects; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000473:pathology*; D051381:Rats; D014018:Tissue Distribution; D014501:Uranium / Q000493:pharmacokinetics / Q000633:toxicity*
D014501:Uranium
Brain development; Dentate gyrus; Heavy metal; Neurogenesis; Telencephalon