Methylmercury (MeHg) is an environmental pollutant known to cause neurobehavio- ral defects, and it is especially toxic to the developing brain. In contrast to the adult, the developing brain consists of a large number of dividing neural progenitor cells (NPCs), which are vulnerable targets for MeHg toxicity. In a previous study, we showed that the embryonic NPCs from the telencephalon are more sensitive to MeHg than other neural cells. Here, we investigated the mechanism of cell death underlying MeHg toxicity. We observed that exposure of NPCs to MeHg caused DNA laddering in a dose- and time- dependent manner. Decreased pro-caspase3 and increased cleaved-caspase3 protein was observed 3-12 hours after incubation of NPCs with MeHg. Moreover, the caspase-inhibitor Z-VAD FMK significantly suppressed MeHg-induced cell death in a dose-dependent manner. These results suggest that environmen¬tally relevant levels of MeHg exposure induce apoptosis in NPCs.
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