Mercury accumulated to the highest levels in the brain (60 ± 28 µg/g wet weight (ww), n = 3), followed by the liver (43 ± 13 µg/g ww, n = 3), and then muscle (6.4 ± 0.1 µg/g ww, n = 3) in zebrafish fed the MeHg diet. In brief, the overall performance of the zebrafish was good and the mortality was low and independent of dietary treatment. General observations and the influence of selenomethionine (SeMet) on the toxicokinetics of MeHg are reported elsewhere. However, in general proteomics studies analysing the effects of MeHg on the brain are scarce, and no proteomics profiling studies currently exist that examine the molecular effects of selenium on the brain proteome or the proposed selenium mediated modulation of MeHg neurotoxicity. For example, calcium signalling and transport pathways were among those most affected in the brain of MeHg exposed common marmoset monkeys. Similar pathways were also at the core of the biological functions affected in MeHg exposed mammalian models of toxicological research. For example, quantitative intact proteomics in Atlantic cod ( Gadus morhua) brain highlighted mitochondrial dysfunction, oxidative stress, and altered calcium homeostasis as key target mechanisms of MeHg-induced neurotoxicity. Proteomics analysis followed by functional and pathway analysis can generate new insights into cellular pathways and functions affected by different classes of toxicants, including metals. Numerous experimental studies have investigated the molecular and cellular mechanisms of MeHg-induced neurotoxicity, but most work to date has focused on specific pathways and few report the systemic effects in the brain. The MeHg-selenol complexes reduce the bioavailability of MeHg and possibly increase the excretion of MeHg from the brain. Another possible mechanism is the formation of MeHg-selenol complexes elevated selenium levels may form MeHg-selenol complexes or lead to ligand exchange with MeHg-complexed thiol residues of proteins. One hypothesis is that appropriate selenium levels uphold optimal antioxidant enzyme activities in cases of MeHg induced oxidative stress. Selenium is an abundant nutrient in fish, and a known antagonist of MeHg toxicity, however the underlying mechanisms are largely unknown. Human health may be both beneficially and adversely affected by this metalloid and the European Food Safety Authority (EFSA) has set an Adequate Intake of 70 µg/day for adults. Selenium, an essential trace element utilised at the active site of a distinct set of proteins termed selenoproteins, is of considerable interest from both a toxicological and nutritional perspective. Analysis of upstream regulators indicated that these changes were linked to the mammalian target of rapamycin (mTOR) pathways, which were activated by MeHg and inhibited by SeMet, possibly through a reactive oxygen species mediated differential activation of RICTOR, the rapamycin-insensitive binding partner of mTOR. The expression levels of proteins associated with gap junction signalling, oxidative phosphorylation, and mitochondrial dysfunction were significantly ( p < 0.05) altered in the brain of zebrafish after exposure to MeHg and SeMet alone or in combination. Mercury concentrations were highest in the brain tissue of MeHg-exposed fish compared to the controls, whereas lower levels of mercury were found in the brain of zebrafish fed both MeHg and SeMet compared with the fish fed MeHg alone. Fish were fed diets containing elevated levels of MeHg and/or SeMet in a 2 × 2 full factorial design for eight weeks. We investigated the influence of selenium (as selenomethionine, SeMet) and MeHg on mercury accumulation and protein expression in the brain of adult zebrafish ( Danio rerio). However, little is known about the molecular mechanisms behind this contaminant-nutrient interaction. The neurotoxicity of methylmercury (MeHg) is well characterised, and the ameliorating effects of selenium have been described.
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