Chronic Exposure to Uranium from Gestation: Effects on Behavior and Neurogenesis in Adulthood.

Céline Dinocourt,Philippe Lestaevel,Christelle Elie,Marie Legrand,Cécile Culeux

doi:10.3390/ijerph14050536

Abstract

Uranium exposure leads to cerebral dysfunction involving for instance biochemical, neurochemical and neurobehavioral effects. Most studies have focused on mechanisms in uranium-exposed adult animals. However, recent data on developing animals have shown that the developing brain is also sensitive to uranium. Models of uranium exposure during brain development highlight the need to improve our understanding of the effects of uranium. In a model in which uranium exposure began from the first day of gestation, we studied the neurobehavioral consequences as well as the progression of hippocampal neurogenesis in animals from dams exposed to uranium. Our results show that 2-month-old rats exposed to uranium from gestational day 1 displayed deficits in special memory and a prominent depressive-like phenotype. Cell proliferation was not disturbed in these animals, as shown by 5-bromo-2′deoxyuridine (BrdU)/neuronal specific nuclear protein (NeuN) immunostaining in the dentate gyrus. However, in some animals, the pyramidal cell layer was dispersed in the CA3 region. From our previous results with the same model, the hypothesis of alterations of neurogenesis at prior stages of development is worth considering, but is probably not the only one. Therefore, further investigations are needed to correlate cerebral dysfunction and its underlying mechanistic pathways.

Highlights

Uranium (U) is an alpha particle-emitting radionuclide of the actinide series and a ubiquitous environmental trace metal found in rocks, soils, water and air [1]
In which U exposure began from the first day of gestation, we recently showed depressive-like behavior in neonatal rats, as well as modifications in the signaling pathways of neuronal cell proliferation and neuronal differentiation during prenatal and postnatal development of the hippocampus [10,11]
Our results show that 2-month-old rats exposed to U from gestational day 1 displayed deficits in special memory and a prominent depressive-like phenotype

Summary

Introduction

Uranium (U) is an alpha particle-emitting radionuclide of the actinide series and a ubiquitous environmental trace metal found in rocks, soils, water and air [1]. U exposure from birth impairs object recognition and memory, causes anxiety and depressive-like behavior in adulthood and disturbs the balance of pro/antioxidant systems [5] and the cholinergic pathway [6]. Studies of animal models show that parental exposure to U during gestation and lactation impairs behaviors such as learning, activity, exploration, and emotionality in offspring [7,8,9]. In which U exposure began from the first day of gestation, we recently showed depressive-like behavior in neonatal rats, as well as modifications in the signaling pathways of neuronal cell proliferation and neuronal differentiation during prenatal and postnatal development of the hippocampus [10,11]. Using the same model to study specific time points allowed us to follow the neurobehavioral consequences as well as the progression of neurogenesis, from

Methods

Results

Conclusion