Effect of uranium on multipotency of neural stem cells in a primary neurosphere culture model

International audienceUranium exposure situations are diverse and originate from its natural presence in the environment, and from its use in specific professional activities in relation with the nuclear industry (extraction, nuclear fuel cycles, and dismantling operations). Uranium internal contamination can occur via ingestion of contaminated food and drinking water or via inhalation of particulate aerosols containing uranium dust. This latest situation is the main cause of contamination in nuclear occupational activities. These contaminations raise concern in terms of potential consequences on human health. They appear to have negative impact on the brain as experimental studies have shown that uranium exposure via ingestion or inhalation can lead to cognitive impairments in rats. Neurogenesis disruption has been proposed to underlie these effects. To address this question, we used in vitro neurosphere primary cultures from rat embryo’s telencephalon at embryonic day 13. We studied uranium impact on multipotency of neural stem cell within a range of concentrations (10, 50, 100 μM) versus control over 7 days of contamination. Our results show a significant effect on cell survival via a decrease of the absolute number of all cell types: neurons, astrocytes and mature oligodendrocytes at 50 and 100 μM. Among cells surviving after 7 days of contamination, analysis of apoptotic gene expression tend to suggest an adaptive response via Bax/Bcl2 balance in favour of cell survival at 100 μM condition, that will need further investigations. In this condition (100 μM), neurons exhibit an aborted morphology with a reduction of the axon and dendrite length correlated with a significant decrease of gene expression GAP43 known to be involved in dendritic arborization development. Regarding gliogenesis, uranium seems to have a direct action on the maintenance of a population of glial progenitors Olig2 positive, linked with a significant increase of NeuroG3 gene expression at 100 μM. All together, these results suggest that uranium exerts a specific action on late cell maturation phases rather than on early determination stages.Keywords: neurotoxicity, stem cell, multipotency, metals, uraniu