title: Methylmercury Induced Neurotoxicity and the Influence of Selenium in the Brains of Adult Zebrafish (Danio rerio).
abstract: The neurotoxicity of methylmercury (MeHg) is well characterised, and the ameliorating effects of selenium have been described. However, little is known about the molecular mechanisms behind this contaminant-nutrient interaction. 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). Fish were fed diets containing elevated levels of MeHg and/or SeMet in a 2 × 2 full factorial design for eight weeks. 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. 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. 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.
authors.affiliation: National Institute of Nutrition and Seafood Research (NIFES), P.O. Box 2029 Nordnes, 5817 Bergen, Norway. josef.rasinger@nifes.no.
authors.forename: Josef Daniel
authors.initials: JD
authors.lastname: Rasinger
authors.affiliation: National Institute of Nutrition and Seafood Research (NIFES), P.O. Box 2029 Nordnes, 5817 Bergen, Norway. anne-katrine.lundebye@nifes.no.
authors.forename: Anne-Katrine
authors.initials: AK
authors.lastname: Lundebye
authors.affiliation: National Institute of Nutrition and Seafood Research (NIFES), P.O. Box 2029 Nordnes, 5817 Bergen, Norway. sampenglase@hotmail.com.|Present address: Aquaculture Research Solutions (ARS), Mundingburra, 4812 QLD, Australia.. sampenglase@hotmail.com.
authors.forename: Samuel James
authors.initials: SJ
authors.lastname: Penglase
authors.affiliation: National Institute of Nutrition and Seafood Research (NIFES), P.O. Box 2029 Nordnes, 5817 Bergen, Norway. stale.ellingsen@uib.no.|Present address: Department of Biology, University of Bergen, P.O. Box 7803, 5020 Bergen, Norway.. stale.ellingsen@uib.no.
authors.forename: Ståle
authors.initials: S
authors.lastname: Ellingsen
authors.affiliation: National Institute of Nutrition and Seafood Research (NIFES), P.O. Box 2029 Nordnes, 5817 Bergen, Norway. heidi.amlund@nifes.no.
authors.forename: Heidi
authors.initials: H
authors.lastname: Amlund
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D017629:Gap Junctions / Q000378:metabolism; D008767:Methylmercury Compounds / Q000493:pharmacokinetics / Q000633:toxicity*; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D010085:Oxidative Phosphorylation; D017382:Reactive Oxygen Species / Q000378:metabolism; D012645:Selenomethionine / Q000493:pharmacokinetics / Q000494:pharmacology*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D014873:Water Pollutants / Q000493:pharmacokinetics / Q000633:toxicity*; D015027:Zebrafish
chemical_list: D008767:Methylmercury Compounds; D017382:Reactive Oxygen Species; D014873:Water Pollutants; D012645:Selenomethionine; D058570:TOR Serine-Threonine Kinases
keywords: contaminant; dietary; exposure; interaction; mechanisms; mercury; methylmercury; nutrient; proteomics; selenium