Manganese Flux Across the Blood–Brain Barrier

Yokel, Robert A.

doi:10.1007/s12017-009-8101-2

Cited by 118 publications

(84 citation statements)

References 136 publications

(167 reference statements)

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“…In biological systems, Mn 2ϩ has the same charge and relative size as Ca 2ϩ , and a number of reports have shown that Mn and Ca trafficking, recruitment, and storage are regulated by the same ion pumps and intracellular compartments. Therefore, Mn 2ϩ might compete with Ca 2ϩ in uptake studies (59,60), thereby disturb intracellular Ca homeostasis and correct tight junction formation and/or localization (26,61). This effect might be reversible by elevated Ca concentrations, as indicated by the present occludin immunofluorescence studies.…”

Section: Discussionmentioning

confidence: 75%

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

Bornhorst

Wehe

Hüwel

et al. 2012

Journal of Biological Chemistry

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Background: Modes of neurotoxic action after Mn overexposure are not fully understood. Results:The blood-CSF barrier showed higher Mn sensitivity and active Mn transport properties. Conclusion:The blood-CSF barrier might be the major route for Mn into the brain. Significance: Deeper insight in the impact of Mn on and its transfer across brain barrier systems might help to prevent irreversible neurological damage.

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Section: Discussionmentioning

confidence: 75%

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

Bornhorst

Wehe

Hüwel

et al. 2012

Journal of Biological Chemistry

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“…Some evidence indicates that both transferrin receptor 1 (TfR1) and the divalent metal transporter 1 (DMT1) contribute to Mn transport across the BBB [45,46]. Other transporters have been reported to possess an ability to transport Mn.…”

Section: Tyrosine Hydroxylase Is Altered Upon Olfactory Mn Exposures mentioning

confidence: 99%

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2015

MOJT

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and anti-oxidant capacities. In particular, manganese superoxide dismutase (MnSOD) catalyzes dismutation of superoxide anion to hydrogen peroxide and molecular oxygen [11]. Manganese is also involved in bone formation and metabolism of amino acids, cholesterol and carbohydrates [12]. While Mn deficiency is rarely observed in humans, Mn exposure is significantly associated with neurobehavioral deficits. Manganese neurotoxicity resembles Parkinson's disease and has been well-documented in people drinking contaminated water, workers employed in mining and Mn ore processing and agricultural workers exposed to Mncontaining pesticide [13]. The use of methylcyclopentadienyl manganese tricarbonyl (MMT), an octane enhancer in gasoline, continues to be a huge concern about potential neurological damage due to inhalable Mn particles after combustion [14] Mn intoxication has also been observed in children under long-term parenteral nutrition and patients with chronic liver diseases [15].Advances in molecular physiology and toxicology have revealed that Mn neurotoxicity is, at least, mediated by dopaminergic dysfunction [16][17][18][19]. The dopaminergic neurotransmission is also impaired by iron deficiency. There is an accumulating body of evidence indicating that iron deficiency reduces dopamine receptor 1 (D 1 R) and D 2 R levels [20][21][22][23]. In addition, extracellular dopamine level is increased in irondeficient animals, which is related to a reduced uptake by AbstractWhile exposures to excessive amounts of metals increase brain damage, our recent study demonstrated that manganese (Mn) exposure corrected neurobehavioral problems resulting from iron deficiency in young rats. To further characterize the dose-dependent effect of intranasal manganese on motor coordination under iron deficiency, weanling rats were fed iron-deficient (5 mg iron/kg diet) or iron-adequate control diet (50 mg/kg) for 5 weeks and manganese chloride (MnCl2) solution was intranasally instilled through the right nostril twice a week for 3 weeks. Iron-deficient rats displayed lower blood hematocrit than controls, reflecting an iron-deficient anemic condition. Mn instillation did not alter hematocrit but modestly decreased body weight. In the rotarod test, Mn-instilled rats decreased motor coordination compared with water-instilled control rats (17% decrease in the time of the first drop; P=0.042). Iron-deficiency also decreased rotarod performance. However, upon Mn instillation, iron-deficient rats stayed longer on the bar by 30% than controls (P=0.006). Interestingly, the improvement in motor coordination was associated with manganese dose. Since both iron and Mn support tyrosine hydroxylase (TH), a critical enzyme in dopamine production, we tested if TH expression was modified by Mn instillation under iron deficiency. TH levels in the striatum were increased in iron deficiency and decreased upon Mn instillation, indicating that TH is unrelated with improved motor coordination in response to olfactory Mn under iron deficiency. Taken together, th...

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“…These facts can also lead to increases in the bioavailability of pollutants in the environment and, consequently, the metal uptake rates and their toxicity (Bervoets et al, 1996;Vergauwen et al, 2013;Lee et al, 2014). Manganese (Mn 2+ ) is a constitutive element of a series of essential enzymes and cofactors that are fundamental to brain function, such as glutamine synthetase, superoxide dismutase and others (Yokel, 2009), but it can be very toxic at concentrations above the optimal threshold level (Vieira et al, 2012). In natural waters, dissolved manganese from anthropogenic sources/influences associated with metal mining and other industrial activities may reach very high concentrations (McNeely et al, 1979;Morillo, Usero, 2008).…”

Section: Introductionmentioning

confidence: 99%

Effects of manganese on fat snook Centropomus parallelus (Carangaria: Centropomidae) exposed to different temperatures

et al. 2017

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This study evaluates the effects of exposure to manganese (Mn 2+ ) for 96 hours at two different temperatures (24 and 27°C) on juveniles of Centropomus parallelus through the activities of glutathione S-transferase (GST) and catalase (CAT), micronuclei test (MN) and comet assay. The GST activity did not show any significant difference between the groups exposed to Mn 2+ and the respective control groups; in contrast, a major increase in the CAT activity was observed at 27°C in the group exposed to Mn 2+ compared to the control group. The genotoxic analyses showed that in all animals exposed to Mn 2+, the number of red cells with micronuclei increased significantly compared to the respective control groups. There was also a significant increase in the incidence of DNA damage in the groups exposed to Mn 2+. At a temperature of 24ºC, animals exposed to Mn 2+ had more DNA damage than those at 27°C. It is likely that the increase in temperature can also induce oxidative stress. Thus, we conclude that manganese is toxic to the fat snook juveniles, causing genotoxic damage, and when associated with an increase in temperature, manganese can also provoke an increase in oxidative stress.Keywords: Biomarkers, DNA damage, Enzymes, Genotoxicity, Metal, Micronuclei.Este estudo avaliou os efeitos da exposição ao manganês (Mn 2+ ), após 96 horas, a duas temperaturas (24 e 27°C) em juvenis de Centropomus parallelus por meio de análises bioquímicas (atividade das enzimas glutationa S-transferase (GST) e catalase (CAT)) e genotóxicas (teste do micronúcleo e ensaio cometa). A atividade da GST não mostrou diferença significativa entre os grupos expostos ao Mn 2+ e os seus respectivos grupos controle, enquanto que um aumento significativo na atividade da CAT foi observado a 27°C no grupo exposto ao Mn 2+ , quando comparado ao grupo controle. As análises genotóxicas mostraram que os animais expostos ao Mn 2+ tiveram aumento significativo na quantidade de células com micronúcleo em relação aos seus grupos de controles. Houve também aumento significativo na incidência de danos ao DNA nos grupos expostos a esse contaminante. Na temperatura de 24°C, os animais expostos ao Mn 2+ tiveram maior quantidade de danos no DNA em relação a 27°C. É provável que o aumento da temperatura também possa induzir o estresse oxidativo. Assim, concluímos que o manganês é tóxico para os juvenis de robalo, causando dano genotóxico, e quando associado a um aumento da temperatura, também pode provocar um aumento no estresse oxidativo.

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Manganese Flux Across the Blood–Brain Barrier

Cited by 118 publications

References 136 publications

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

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

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Effects of manganese on fat snook Centropomus parallelus (Carangaria: Centropomidae) exposed to different temperatures

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