Mercury accumulates in all neural cells, yet methylmercury (MeHg) seems to preferentially accumulate in glial cells, such as astrocytes and microglia. Both the cell types are known targets of MeHg poisonings. Recent studies suggest that these cell types exhibit cell-specific responses to this organometal on a highly variable and distinct temporal axis. In general, in vitro cell culture studies have shown that induction of reactive oxygen species (ROS) generation and attenuation of intracellular glutathione (GSH) levels occur most rapidly in microglia, and within minutes of exposure. In contrast, the astrocytes respond on a more protracted time course (hours, not minutes). Our recent studies also suggest that a key regulatory transcription factor NF-E2-related factor 2 (Nrf2) is upregulated and translocated into the microglial nucleus within minutes of exposure to MeHg, while in astrocytes the response occurs at a later time point (hours post exposure). Combined with evidence microglia accumulate significantly higher MeHg levels and possess a lower reductive capacity (e.g., GSH levels) vs. astrocytes, we posit that the unique sensitivities of the two cell types to MeHg reflects cell-specific biochemical and physiological characteristics.
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