Étude de l’effet de l’uranium sur la multipotentialité des cellules souches neurales : modèle in vitro de culture de neurosphères

Abstract : Uranium (U) is a heavy metal naturally present in earth crust. Human activities (extraction, use in nuclear fuel cycles) can lead to environment dispersal. U can then be found in drinking water and food and represents a rising concern about consequences on human health. Experimental studies have shown that U exposure by ingestion can cause cognitive impairment. A neurogenesis disruption could explain such effects. Using in vitro neurosphere primary cultures from embryo’s telencephalon at E13, we studied U impact on neural stem cell (NSC) multipotentiality 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 in vitro, analysis of apoptotic gene expression tend to reveal an adaptative response via Bax/Bcl2 balance in favour of cell survival at 100 µM condition that will need further investigations. After 7 days of contamination at 100 µM, neurons exhibit an aborted morpholgy 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, U seem to have a direct action on the maintenance of a population of glial progenitors olig2+ linked with a significant increase of NeuroG3 gene expression at 100 µM. All together, these results suggest that U exerts a specific action on late cell maturation phases rather than on early determination stages.
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Master Thesis
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Submitted on : Tuesday, December 12, 2017 - 6:25:16 PM
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Antoine Becquet. Étude de l’effet de l’uranium sur la multipotentialité des cellules souches neurales : modèle in vitro de culture de neurosphères. Sciences pharmaceutiques. 2017. ⟨dumas-01662196⟩



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