@phdthesis{Lohren2015, author = {Lohren, Hanna}, title = {Mechanisms of mercury species-mediated neurotoxicity}, school = {Universit{\"a}t Potsdam}, pages = {141, viii}, year = {2015}, language = {en} } @article{LohrenBlagojevicFitkauetal.2015, author = {Lohren, Hanna and Blagojevic, Lara and Fitkau, Romy and Ebert, Franziska and Schildknecht, Stefan and Leist, Marcel and Schwerdtle, Tanja}, title = {Toxicity of organic and inorganic mercury species in human neurons and human astrocytes}, series = {Journal of trace elements in medicine and biology}, volume = {32}, journal = {Journal of trace elements in medicine and biology}, publisher = {Elsevier}, address = {Jena}, issn = {0946-672X}, doi = {10.1016/j.jtemb.2015.06.008}, pages = {200 -- 208}, year = {2015}, 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.}, language = {en} } @article{LohrenBornhorstGallaetal.2015, author = {Lohren, Hanna and Bornhorst, Julia and Galla, Hans-Joachim and Schwerdtle, Tanja}, title = {The blood-cerebrospinal fluid barrier - first evidence for an active transport of organic mercury compounds out of the brain}, series = {Metallomics : integrated biometal science}, volume = {7}, journal = {Metallomics : integrated biometal science}, number = {10}, publisher = {Royal Society of Chemistry}, address = {Cambridge}, issn = {1756-5901}, doi = {10.1039/c5mt00171d}, pages = {1420 -- 1430}, year = {2015}, abstract = {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.}, language = {en} } @misc{LohrenBornhorstGallaetal.2015, author = {Lohren, Hanna and Bornhorst, Julia and Galla, Hans-Joachim and Schwerdtle, Tanja}, title = {The blood-cerebrospinal fluid barrier}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-82089}, year = {2015}, abstract = {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.}, language = {en} } @article{LohrenBornhorstGallaetal.2015, author = {Lohren, Hanna and Bornhorst, Julia and Galla, Hans-Joachim and Schwerdtle, Tanja}, title = {The blood-cerebrospinal fluid barrier}, series = {Metallomics : integrated biometal science}, volume = {10}, journal = {Metallomics : integrated biometal science}, number = {7}, publisher = {Royal Society of Chemistry}, address = {Cambridge}, issn = {1756-5901}, doi = {10.1039/C5MT00171D}, pages = {1420 -- 1430}, year = {2015}, abstract = {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.}, language = {en} }