Host: The Japanese Society of Toxicology
Name : The 50th Annual Meeting of the Japanese Society of Toxicology
Date : June 19, 2023 - June 21, 2023
Methylmercury is one of the most common environmental contaminants causing neurological disorders in the brain. In recent years, fetal health hazards due to exposure of pregnant women to methylmercury via fish diets are a worldwide concern. However, the mechanisms involved in methylmercury-induced neurological damage remain largely unknown. We have previously shown that methylmercury induces cell death via induction of expression of inflammatory cytokines such as oncostatin M (OSM), TNF-α, IL-1β, and CCL2, using mouse neural stem cell lines. We also found that the above proinflammatory cytokines are induced in microglia in the brains of mice treated with methylmercury. Moreover, OSM released from microglia induces cell death by binding to the extracellular domain of TNF receptor 3 (TNFR3) on neuronal cell membranes, and that this process is promoted by the direct binding of methylmercury to the 105th cysteine residue in OSM. Recently, we have shown that treatment of mouse brain slices with methylmercury induces neuronal cell death, which is inhibited by treatment with liposome encapsulated clodronate that selectively kill microglia. Mice exposed to methylmercury also showed impaired memory function, but this impairment was also suppressed by simultaneous administration of PLX3397, a microglia inhibitor. As described above, it has been suggested that methylmercury may damage surrounding neurons through induction of expression and production of inflammatory cytokines by activating microglia. This talk will introduce the role of microglia in methylmercury-induced neurological damage in the brain.
