title: Impact of manganese on and transfer across blood-brain and blood-cerebrospinal fluid barrier in vitro.
abstract: Manganese occupational and dietary overexposure has been shown to result in specific clinical central nervous system syndromes, which are similar to those observed in Parkinson disease. To date, modes of neurotoxic action of Mn are still to be elucidated but are thought to be strongly related to Mn accumulation in brain and oxidative stress. However, the pathway and the exact process of Mn uptake in the brain are yet not fully understood. Here, two well characterized primary porcine in vitro models of the blood-brain and the blood-cerebrospinal fluid (CSF) barrier were applied to assess the transfer of Mn in the brain while monitoring its effect on the barrier properties. Thus, for the first time effects of MnCl(2) on the integrity of these two barriers as well as Mn transfer across the respective barriers are compared in one study. The data reveal a stronger Mn sensitivity of the in vitro blood-CSF barrier compared with the blood-brain barrier. Very interestingly, the negative effects of Mn on the structural and functional properties of the highly Mn-sensitive blood-CSF barrier were partly reversible after incubation with calcium. In summary, both the observed stronger Mn sensitivity of the in vitro blood-CSF barrier and the observed site-directed, most probably active, Mn transport toward the brain facing compartment, reveal that, in contrast to the general assumption in literature, after oral Mn intake the blood-CSF barrier might be the major route for Mn into the brain.
authors.affiliation: Graduate School of Chemistry, the University of Münster, 48149 Münster, Germany; Institute of Food Chemistry, the University of Münster, 48149 Münster, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Bornhorst
authors.affiliation: Institute of Inorganic and Analytical Chemistry, the University of Münster, 48149 Münster, Germany.
authors.forename: Christoph A
authors.initials: CA
authors.lastname: Wehe
authors.affiliation: Institute of Biochemistry, the University of Münster, 48149 Münster, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Hüwel
authors.affiliation: Institute of Inorganic and Analytical Chemistry, the University of Münster, 48149 Münster, Germany.
authors.forename: Uwe
authors.initials: U
authors.lastname: Karst
authors.affiliation: Institute of Biochemistry, the University of Münster, 48149 Münster, Germany.
authors.forename: Hans-Joachim
authors.initials: HJ
authors.lastname: Galla
authors.affiliation: Institute of Food Chemistry, the University of Münster, 48149 Münster, Germany. Electronic address: tanja.schwerdtle@uni-muenster.de.
authors.forename: Tanja
authors.initials: T
authors.lastname: Schwerdtle
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism* / Q000473:pathology; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D002712:Chlorides / Q000633:toxicity*; D017136:Ion Transport / Q000187:drug effects; D008345:Manganese / Q000633:toxicity; D017895:Manganese Compounds; D008954:Models, Biological; D010302:Parkinson Disease, Secondary / Q000134:cerebrospinal fluid* / Q000139:chemically induced* / Q000473:pathology; D013552:Swine
chemical_list: D002712:Chlorides; D017895:Manganese Compounds; D008345:Manganese; C025340:manganese chloride; D002118:Calcium