title: Toxicity of organic and inorganic mercury species in differentiated human neurons and human astrocytes.
abstract: Organic mercury (Hg) species exert their toxicity primarily in the central nervous system. The food relevant Hg species methylmercury (MeHg) has been frequently studied regarding its neurotoxic effects in vitro and in vivo. Neurotoxicity of thiomersal, which is used as a preservative in medical preparations, is to date less characterised. Due to dealkylation of organic Hg or oxidation of elemental Hg, inorganic Hg is present in the brain albeit these species are not able to readily cross the blood brain barrier. This study compared for the first time toxic effects of organic MeHg chloride (MeHgCl) and thiomersal as well as inorganic mercury chloride (HgCl2) in differentiated human neurons (LUHMES) and human astrocytes (CCF-STTG1). The three Hg species differ in their degree and mechanism of toxicity in those two types of brain cells. Generally, neurons are more susceptible to Hg species induced cytotoxicity as compared to astrocytes. This might be due to the massive cellular mercury uptake in the differentiated neurons. The organic compounds exerted stronger cytotoxic effects as compared to inorganic HgCl2. In contrast to HgCl2 exposure, organic Hg compounds seem to induce the apoptotic cascade in neurons following low-level exposure. No indicators for apoptosis were identified for both inorganic and organic mercury species in astrocytes. Our studies clearly demonstrate species-specific toxic mechanisms. A mixed exposure towards all Hg species in the brain can be assumed. Thus, prospectively coexposure studies as well as cocultures of neurons and astrocytes could provide additional information in the investigation of Hg induced neurotoxicity.
authors: Department of Food Chemistry, Institute of Nutritional Science, University of Potsdam, Arthur-Scheunert-Allee 114 - 116, 14558 Nuthetal, Germany. Electronic address: lohren@uni-potsdam.de.
authors: Hanna
authors: H
authors: Lohren
authors: Institute of Food Chemistry, University of Muenster, Corrensstraße 45, 48149 Muenster, Germany. Electronic address: blagojevic@igzev.de.
authors: Lara
authors: L
authors: Blagojevic
authors: Department of Food Chemistry, Institute of Nutritional Science, University of Potsdam, Arthur-Scheunert-Allee 114 - 116, 14558 Nuthetal, Germany. Electronic address: fitkau@gmx.de.
authors: Romy
authors: R
authors: Fitkau
authors: Department of Food Chemistry, Institute of Nutritional Science, University of Potsdam, Arthur-Scheunert-Allee 114 - 116, 14558 Nuthetal, Germany. Electronic address: fraebert@uni-potsdam.de.
authors: Franziska
authors: F
authors: Ebert
authors: Doerenkamp-Zbinden Chair of In Vitro Toxicology and Biomedicine, University of Konstanz, Universitaetsstraße 10, 78464 Konstanz, Germany. Electronic address: stefan.schildknecht@uni-konstanz.de.
authors: Stefan
authors: S
authors: Schildknecht
authors: Doerenkamp-Zbinden Chair of In Vitro Toxicology and Biomedicine, University of Konstanz, Universitaetsstraße 10, 78464 Konstanz, Germany. Electronic address: marcel.leist@uni-konstanz.de.
authors: Marcel
authors: M
authors: Leist
authors: Department of Food Chemistry, Institute of Nutritional Science, University of Potsdam, Arthur-Scheunert-Allee 114 - 116, 14558 Nuthetal, Germany. Electronic address: tanja.schwerdtle@uni-potsdam.de.
authors: Tanja
authors: T
authors: Schwerdtle
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D001253:Astrocytes / Q000166:cytology* / Q000187:drug effects; D001682:Biological Availability; D053148:Caspase 3 / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects*; D002478:Cells, Cultured; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D008247:Lysosomes / Q000187:drug effects / Q000378:metabolism; D008627:Mercuric Chloride / Q000633:toxicity*; D008767:Methylmercury Compounds / Q000633:toxicity*; D008856:Microscopy, Fluorescence; D009474:Neurons / Q000166:cytology* / Q000187:drug effects; D013849:Thimerosal / Q000633:toxicity*
chemical_list: D008767:Methylmercury Compounds; D013849:Thimerosal; D008627:Mercuric Chloride; D053148:Caspase 3; C004925:methylmercuric chloride
keywords: Apoptosis; Cytotoxicity; Human differentiated neurons; Mercuric mercury; Methylmercury; Thiomersal