Impact of Manganese on and Transfer across Blood-Brain and Blood-Cerebrospinal Fluid Barrier in Vitro

Bornhorst, Julia; Wehe, Christoph A.; Hüwel, Sabine; Kärst, Uwe; Galla, Hans‐Joachim; Schwerdtle, Tanja

doi:10.1074/jbc.m112.344093

Cited by 72 publications

(69 citation statements)

References 58 publications

(64 reference statements)

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“…At early phase, M1 macrophages appear to remove injured vascular endothelial cells by phagocytosis (Jackson, 2011;Phillipson and Kubes, 2011); however, under insufficient M2 condition, M1 macrophages can probably induce prolonged inflammation and destruction of BBB. The BBB possesses manganese sensitivity (Bornhorst et al, 2012), suggesting that disequilibrium of iron and manganese levels is presumably associated with dysfunction of BBB directly. Imbalance of zinc and copper levels may contribute to dysfunction of astrocytes because astrocytes express copper, zinc (CuZn) superoxide dismutase-1 (SOD-1) activity (Chen et al, 2006).…”

Section: Downloaded Frommentioning

confidence: 99%

Involvement of Neuroinflammation during Brain Development in Social Cognitive Deficits in Autism Spectrum Disorder and Schizophrenia

Nakagawa¹,

Chiba²

2016

Journal of Pharmacology and Experimental Therapeutics

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Development of social cognition, a unique and high-order function, depends on brain maturation from childhood to adulthood in humans. Autism spectrum disorder (ASD) and schizophrenia have similar social cognitive deficits, although age of onset in each disorder is different. Pathogenesis of these disorders is complex and contains several features, including genetic risk factors, environmental risk factors, and sites of abnormalities in the brain. Although several hypotheses have been postulated, they seem to be insufficient to explain how brain alterations associated with symptoms in these disorders develop at distinct developmental stages. Development of ASD appears to be related to cerebellar dysfunction and subsequent thalamic hyperactivation in early childhood. By contrast, schizophrenia seems to be triggered by thalamic hyperactivation in late adolescence, whereas hippocampal aberration has been possibly initiated in childhood. One of the possible culprits is metal homeostasis disturbances that can induce dysfunction of blood-cerebrospinal fluid barrier. Thalamic hyperactivation is thought to be induced by microglia-mediated neuroinflammation and abnormalities of intracerebral environment. Consequently, it is likely that the thalamic hyperactivation triggers dysregulation of the dorsolateral prefrontal cortex for lower brain regions related to social cognition. In this review, we summarize the brain aberration in ASD and schizophrenia and provide a possible mechanism underlying social cognitive deficits in these disorders based on their distinct ages of onset.

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Section: Downloaded Frommentioning

confidence: 99%

Involvement of Neuroinflammation during Brain Development in Social Cognitive Deficits in Autism Spectrum Disorder and Schizophrenia

Nakagawa¹,

Chiba²

2016

Journal of Pharmacology and Experimental Therapeutics

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“…18,19 The PCPECs were seeded on microporous Transwell s filter inserts (1.12 cm 2 growth area, 0.4 mM pore size; Corning, Wiesbaden, Germany) and cultivated as described before. 18 …”

Section: Methodsmentioning

confidence: 99%

“…18 After 8 days of proliferation (DIV 1-9) and 6 days of differentiation under serum free conditions (DIV 9-14) the cells built up a tight barrier and obtained functions mimicking the in vivo situation. 20 In correspondence with the secretion of cerebrospinal fluid in vivo, fully differentiated cells transfer cell culture medium from the basolateral (blood facing) to the apical (CSF facing) compartment.…”

Section: Cytotoxicity Testingmentioning

confidence: 99%

“…The clearance of phenol red against a concentration gradient is indicative for fully developed transfer properties and the tightness of the barrier. 18,20 On DIV 14 the respective mercury compounds were applied in a concentration range of 0.01-8 mM (MeHgCl and thiomersal) or 0.01-60 mM (HgCl 2 ) either on the basolateral or on the apical or on both sides simultaneously by replacing 10% of the culture medium with fresh mercury compounds containing medium in the respective compartment. During 72 h of incubation, the transepithelial electrical resistance (TEER) was monitored as parameter for the integrity of the barrier by the cellZscope s (nanoAnalytics, Münster, Germany).…”

Section: Cytotoxicity Testingmentioning

confidence: 99%

“…18 Briefly, 1 mg mL À1 mouse anti occludin (Zytomed, Berlin, Germany) as first antibody and alexa fluor s 546 goat anti-mouse (Invitrogen, Paisley, UK) as secondary antibody were incubated in 0.5% bovine serum albumin solution (BSA, Roth) at 37 1C for 30 min. Additionally, cell nuclei were stained with 10 mg mL À1 Hoechst 33258 (Bisbenzimide, Sigma Aldrich) for 0.5 min before the filters were mounted in aqua poly/mount (Polysciences, Washington, USA).…”

Section: Immunocytochemical Stainingmentioning

confidence: 99%

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Blood-Cerebrospinal Fluid Barrier

Gibbs¹,

Thomas²

2015

Encyclopedia of Psychopharmacology

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U n i v e r s i t ä t P o t s d a mPostprints der Universität Potsdam Mathematisch-Naturwissenschaftliche Reihe ; 200 1420 | Metallomics, 2015 , 7, 1420 --1430 This journal is © The Royal Society of Chemistry 2015Cite this: Metallomics, 2015, 7, 1420The blood-cerebrospinal fluid barrier -first evidence for an active transport of organic mercury compounds out of the brain Hanna Lohren, a Julia Bornhorst, a Hans-Joachim Galla b and Tanja Schwerdtle* a 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.

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