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Human Pluripotent Stem Cell Based Developmental Toxicity Assays for Chemical Safety Screening and Systems Biology Data Generation
Published on: June 17, 2015
Cellular Conditions Responsible for Methylmercury-Mediated Neurotoxicity
Masatake Fujimura1, Fusako Usuki2
1Department of Basic Medical Sciences, National Institute for Minamata Disease, Kumamoto 867-0008, Japan.
Abstract:
Methylmercury (MeHg) is a widely known environmental pollutant that causes severe neurotoxicity. MeHg-induced neurotoxicity depends on various cellular conditions, including differences in the characteristics of tissues and cells, exposure age (fetal, childhood, or adulthood), and exposure levels. Research has highlighted the importance of oxidative stress in the pathogenesis of MeHg-induced toxicity and the site- and cell-specific nature of MeHg-induced neurotoxicity. The cerebellar granule cells and deeper layer cerebrocortical neurons are vulnerable to MeHg. In contrast, the hippocampal neurons are resistant to MeHg, even at high mercury accumulation levels. This review summarizes the mechanisms underlying MeHg-mediated intracellular events that lead to site-specific neurotoxicity. Specifically, we discuss the mechanisms associated with the redox ability, neural outgrowth and synapse formation, cellular signaling pathways, epigenetics, and the inflammatory conditions of microglia.
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