Environmental toxicants such as methylmercury play a critical role in the pathogenesis of many neurodevelopmental disorders. Environmental exposure to methylmercury frequently occurs at low doses, most frequently through fish consumption. Although the general population is at risk for exposure, pregnant women and young children are the most vulnerable. A common symptom of perinatal exposure to methylmercury is increased sensory (visual) deficits, motor impairment, and an overall cognitive decline. Research has indicated that the developing cerebellum, specifically the cerebellar granular layer, is particularly vulnerable to methylmercury neurotoxicity. This review examines the effects of low-level methylmercury exposure on motor coordination. We specifically focus on the role of cerebellar granule cells in methylmercury neurotoxicity. We suggest that methylmercury induces oxidative stress in cerebellar granule cells, which subsequently results in apoptotic cell death. Understanding the mechanism by which methylmercury induces toxicity within the developing brain will allow for enhanced treatments and potential reversal of the detrimental effects.
Keywords: AIF; Apoptosis; Cerebellar granule cells; GPx; GSH; GSSG; MTP; Methylmercury; NBAS; Neonatal Behavioral Assessment Scale; Nrf2; Oxidative stress; PARP; PCBs; TrxR; apoptosis-inducing factor; endoG; endonucleaese G; glutathione; glutathione disulfide; glutathione peroxidase; mitochondrial permeability transition pore; nuclear factor erythroid 2-related factor 2; poly-ADP ribose polymerase; polychlorinated biphenyls; thioredoxin reductase.
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