TY - JOUR A1 - Lohren, Hanna A1 - Bornhorst, Julia A1 - Fitkau, Romy A1 - Pohl, Gabriele A1 - Galla, Hans-Joachim A1 - Schwerdtle, Tanja T1 - Effects on and transfer across the blood-brain barrier in vitro-Comparison of organic and inorganic mercury species JF - BMC pharmacology & toxicology N2 - Background: Transport of methylmercury (MeHg) across the blood-brain barrier towards the brain side is well discussed in literature, while ethylmercury (EtHg) and inorganic mercury are not adequately characterized regarding their entry into the brain. Studies investigating a possible efflux out of the brain are not described to our knowledge. Methods: This study compares, for the first time, effects of organic methylmercury chloride (MeHgCl), EtHg-containing thiomersal and inorganic Hg chloride (HgCl2) on as well as their transfer across a primary porcine in vitro model of the blood-brain barrier. Results: With respect to the barrier integrity, the barrier model exhibited a much higher sensitivity towards HgCl2 following basolateral incubation (brain-facing side) as compared to apical application (blood-facing side). These HgCl2 induced effects on the barrier integrity after brain side incubation are comparable to that of the organic species, although MeHgCl and thiomersal exerted much higher cytotoxic effects in the barrier building cells. Hg transfer rates following exposure to organic species in both directions argue for diffusion as transfer mechanism. Inorganic Hg application surprisingly resulted in a Hg transfer out of the brain-facing compartment. Conclusions: In case of MeHgCl and thiomersal incubation, mercury crossed the barrier in both directions, with a slight accumulation in the basolateral, brain-facing compartment, after simultaneous incubation in both compartments. For HgCl2, our data provide first evidence that the blood-brain barrier transfers mercury out of the brain. KW - Organic mercury KW - Inorganic mercury KW - Methylmercury KW - Thiomersal KW - Mercuric mercury KW - In vitro blood-brain barrier model Y1 - 2016 U6 - https://doi.org/10.1186/s40360-016-0106-5 SN - 2050-6511 VL - 17 SP - 422 EP - 433 PB - BioMed Central CY - London ER - 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 - 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 - 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 - 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 - Fitkau, Romy A1 - Pohl, Gabriele A1 - Galla, Hans-Joachim A1 - Schwerdtle, Tanja T1 - Effects on and transfer across the blood-brain barrier in vitro BT - Comparison of organic and inorganic mercury species N2 - Background: Transport of methylmercury (MeHg) across the blood-brain barrier towards the brain side is well discussed in literature, while ethylmercury (EtHg) and inorganic mercury are not adequately characterized regarding their entry into the brain. Studies investigating a possible efflux out of the brain are not described to our knowledge. Methods: This study compares, for the first time, effects of organic methylmercury chloride (MeHgCl), EtHg-containing thiomersal and inorganic Hg chloride (HgCl2) on as well as their transfer across a primary porcine in vitro model of the blood-brain barrier. Results: With respect to the barrier integrity, the barrier model exhibited a much higher sensitivity towards HgCl2 following basolateral incubation (brain-facing side) as compared to apical application (blood-facing side). These HgCl2 induced effects on the barrier integrity after brain side incubation are comparable to that of the organic species, although MeHgCl and thiomersal exerted much higher cytotoxic effects in the barrier building cells. Hg transfer rates following exposure to organic species in both directions argue for diffusion as transfer mechanism. Inorganic Hg application surprisingly resulted in a Hg transfer out of the brain-facing compartment. Conclusions: In case of MeHgCl and thiomersal incubation, mercury crossed the barrier in both directions, with a slight accumulation in the basolateral, brain-facing compartment, after simultaneous incubation in both compartments. For HgCl2, our data provide first evidence that the blood-brain barrier transfers mercury out of the brain. T3 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 406 KW - organic mercury KW - inorganic mercury KW - methylmercury KW - thiomersal KW - mercuric mercury KW - in vitro blood-brain barrier model Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-401776 ER -