TY - THES A1 - Lohren, Hanna T1 - Mechanisms of mercury species-mediated neurotoxicity BT - transfer across brain brain barriers and toxicity in brain-associated cells Y1 - 2015 ER - TY - JOUR A1 - Lohren, Hanna A1 - Blagojevic, Lara A1 - Fitkau, Romy A1 - Ebert, Franziska A1 - Schildknecht, Stefan A1 - Leist, Marcel A1 - Schwerdtle, Tanja T1 - Toxicity of organic and inorganic mercury species in human neurons and human astrocytes JF - Journal of trace elements in medicine and biology N2 - 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. KW - Methylmercury KW - Thiomersal KW - Mercuric mercury KW - Human differentiated neurons KW - Cytotoxicity KW - Apoptosis Y1 - 2015 U6 - https://doi.org/10.1016/j.jtemb.2015.06.008 SN - 0946-672X VL - 32 SP - 200 EP - 208 PB - Elsevier CY - Jena ER - TY - JOUR A1 - Lohren, Hanna A1 - Bornhorst, Julia A1 - Galla, Hans-Joachim A1 - Schwerdtle, Tanja T1 - The blood-cerebrospinal fluid barrier - first evidence for an active transport of organic mercury compounds out of the brain JF - Metallomics : integrated biometal science N2 - Exposure to organic mercury compounds promotes primarily neurological effects. Although methylmercury is recognized as a potent neurotoxicant, its transfer into the central nervous system (CNS) is not fully evaluated. While methylmercury and thiomersal pass the blood-brain barrier, limited data are available regarding the second brain regulating interface, the blood-cerebrospinal fluid (CSF) barrier. This novel study was designed to investigate the effects of organic as well as inorganic mercury compounds on, and their transfer across, a porcine in vitro model of the blood-CSF barrier for the first time. The barrier system is significantly more sensitive towards organic Hg compounds as compared to inorganic compounds regarding the endpoints cytotoxicity and barrier integrity. Whereas there are low transfer rates from the blood side to the CSF side, our results strongly indicate an active transfer of the organic mercury compounds out of the CSF. These results are the first to demonstrate an efflux of organic mercury compounds regarding the CNS and provide a completely new approach in the understanding of mercury compounds specific transport. Y1 - 2015 U6 - https://doi.org/10.1039/c5mt00171d SN - 1756-5901 SN - 1756-591X VL - 7 IS - 10 SP - 1420 EP - 1430 PB - Royal Society of Chemistry CY - Cambridge ER - TY - GEN A1 - Lohren, Hanna A1 - Bornhorst, Julia A1 - Galla, Hans-Joachim A1 - Schwerdtle, Tanja T1 - The blood–cerebrospinal fluid barrier BT - First evidence for an active transport of organic mercury compounds out of the brain N2 - Exposure to organic mercury compounds promotes primarily neurological effects. Although methylmercury is recognized as a potent neurotoxicant, its transfer into the central nervous system (CNS) is not fully evaluated. While methylmercury and thiomersal pass the blood–brain barrier, limited data are available regarding the second brain regulating interface, the blood–cerebrospinal fluid (CSF) barrier. This novel study was designed to investigate the effects of organic as well as inorganic mercury compounds on, and their transfer across, a porcine in vitro model of the blood–CSF barrier for the first time. The barrier system is significantly more sensitive towards organic Hg compounds as compared to inorganic compounds regarding the endpoints cytotoxicity and barrier integrity. Whereas there are low transfer rates from the blood side to the CSF side, our results strongly indicate an active transfer of the organic mercury compounds out of the CSF. These results are the first to demonstrate an efflux of organic mercury compounds regarding the CNS and provide a completely new approach in the understanding of mercury compounds specific transport. T3 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 200 Y1 - 2015 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-82089 ER - TY - JOUR A1 - Lohren, Hanna A1 - Bornhorst, Julia A1 - Galla, Hans-Joachim A1 - Schwerdtle, Tanja T1 - The blood–cerebrospinal fluid barrier BT - First evidence for an active transport of organic mercury compounds out of the brain JF - Metallomics : integrated biometal science N2 - Exposure to organic mercury compounds promotes primarily neurological effects. Although methylmercury is recognized as a potent neurotoxicant, its transfer into the central nervous system (CNS) is not fully evaluated. While methylmercury and thiomersal pass the blood–brain barrier, limited data are available regarding the second brain regulating interface, the blood–cerebrospinal fluid (CSF) barrier. This novel study was designed to investigate the effects of organic as well as inorganic mercury compounds on, and their transfer across, a porcine in vitro model of the blood–CSF barrier for the first time. The barrier system is significantly more sensitive towards organic Hg compounds as compared to inorganic compounds regarding the endpoints cytotoxicity and barrier integrity. Whereas there are low transfer rates from the blood side to the CSF side, our results strongly indicate an active transfer of the organic mercury compounds out of the CSF. These results are the first to demonstrate an efflux of organic mercury compounds regarding the CNS and provide a completely new approach in the understanding of mercury compounds specific transport. Y1 - 2015 U6 - https://doi.org/10.1039/C5MT00171D SN - 1756-5901 SN - 1756-591X VL - 10 IS - 7 SP - 1420 EP - 1430 PB - Royal Society of Chemistry CY - Cambridge ER -