Methylmercury induces the expression of TNF-α selectively in the brain of mice

Methylmercury selectively damages the central nervous system (CNS). The tumor necrosis factor (TNF) superfamily includes representative cytokines that participate in the inflammatory response as well as cell survival, and apoptosis. In this study, we found that administration of methylmercury selectively induced TNF-alpha expression in the brain of mice. Although the accumulated mercury concentration in the liver and kidneys was greater than in the brain, TNF-alpha expression was induced to a greater extent in brain. Thus, it is possible that there may exist a selective mechanism by which methylmercury induces TNF-alpha expression in the brain. We also found that TNF-alpha expression was induced by methylmercury in C17.2 cells (mouse neural stem cells) and NF-kappa B may participate as a transcription factor in that induction. Further, we showed that the addition of TNF-alpha antagonist (WP9QY) reduced the toxicity of methylmercury to C17.2 cells. In contrast, the addition of recombinant TNF-alpha to the culture medium decreased the cell viability. We suggest that TNF-alpha may play a part in the selective damage of the CNS by methylmercury. Furthermore, our results indicate that the higher TNF-alpha expression induced by methylmercury maybe the cause of cell death, as TNF-alpha binds to its receptor after being released extracellularly.