Mitochondrial-dependent manganese neurotoxicity in rat primary astrocyte cultures

Yin, Zhaoobao; Aschner, Judy L.; Santos, Ana Paula dos; Aschner, Michael

doi:10.1016/j.brainres.2008.01.079

Cited by 117 publications

(100 citation statements)

References 86 publications

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“…Shukla [9] have demonstrated a concentration-dependent effect of Mn on the brain microsomal Mg Apoptosis has been shown to be involved in Mn-induced neurotoxicity. Mn-exposure triggered apoptosis and cell death via the ERK signaling pathway [10]. The present study demonstrated that dietary Mn induced similar apoptosis in the brain region, as was observed following Mn administration in previous studies.…”

Section: Discussionsupporting

confidence: 89%

Effects of Dietary Manganese on Oxidative Damage of the Neurons in Cocks

Liu¹,

Jing²,

Xue³

et al. 2015

Proceedings of the 2015 International Conference on Materials, Environmental and Biological Engineering

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Abstract. To investigate the Manganese(Mn)-induced toxicity on crucial oxidative damage parameters on brain of birds, 50-day-old male Hyline cocks were fed either a commercial diet or a Mn-supplemented diet. The following were determined: restraining ability to OH·, the activities of Na+-K+-ATPase, Mg 2+ -ATPase and Ca 2+ -ATPase, the activities of succinate dehydrogenase (SDH) and Calcineurin (CaN); Exposure to Mn significantly lowered restraining ability to OH·, the activities of ATP enzymes, activities of SDH and CaN. These findings suggested that Mn exposure resulted in the oxidative damage of cock cerebral tissue.

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Section: Discussionsupporting

confidence: 89%

Effects of Dietary Manganese on Oxidative Damage of the Neurons in Cocks

Liu¹,

Jing²,

Xue³

et al. 2015

Proceedings of the 2015 International Conference on Materials, Environmental and Biological Engineering

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“…The mechanism of neurotoxicity appears multifactorial. Astrocytic dysfunction occurs due to their high affinity transport system accumulating high intracellular concentrations of Mn (Yin et al, 2008). Manganese also causes microglial activation by induction of cytokines and reactive oxygen species (Dodd and Filipov, 2011), as well as causing disruption of several neurotransmitters and mitochondrial dysfunction, culminating in neuronal apoptosis (Smith et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

Investigation of manganese homeostasis in dogs with anaemia and chronic enteropathy

Ferreira¹,

Aylor²,

Mellanby³

et al. 2018

Open Vet J.

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Lethargy is a frequent and important clinical feature of anaemia; however, it does not absolutely correlate with the severity of anaemia. Manganese is efficiently absorbed through the gastrointestinal tract via divalent metal transporter 1 (DMT1), which is also responsible for iron transport. DMT1 is upregulated in iron deficiency (ID). Increased manganese concentrations are reported in ID anaemia (IDA) in various species. Manganese is neurotoxic and therefore may contribute to lethargy observed in some anaemic patients. In addition, anaemia and ID are common in human inflammatory bowel disease. Little is known about how anaemia influences manganese metabolism in veterinary patients and how common is anaemia in dogs with chronic enteropathy (CE). If elevated manganese concentrations are found, then potentially neurotoxicity may be contributing to morbidity in these cases. The objectives of this study were to investigate the hypothesis that whole blood manganese concentrations would be increased in dogs with anaemia, particularly in dogs with confirmed IDA, and that anaemia would be common in canine CE. Medical records from 2012-2016 were reviewed for dogs with CE that were anaemic, as well as dogs with confirmed IDA, where a sample suitable for manganese analysis was held in an archive. Manganese concentration was measured in whole blood from: 11 anaemic dogs with CE, 6 dogs with IDA, 9 non-anaemic ill controls, and 12 healthy controls. MannWhitney U and Kruskal-Wallis tests with post-test Dunn's multiple comparisons tests were performed, with P<0.05 considered significant. The prevalence of anaemia in canine CE was 20.6% (33/160). Manganese concentrations were significantly different between all groups (P=0.0001) and higher in non-anaemic than anaemic dogs (P=0.0078). Manganese concentrations were also higher in healthy compared to ill controls (P<0.0001), anaemic dogs with CE (P=0.0056) and to dogs with IDA (P=0.0001). No differences were observed between anaemic dogs with CE, IDA and ill controls. Although anaemia was frequently observed in canine CE, the hypothesis that dogs with anaemia would have increased manganese concentrations, possibly contributing to a lethargic state was not supported. Further research is warranted to understand the influence of anaemia on whole blood manganese.

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“…It has been reported that Mn enters the mitochondria via a mitochondrial Ca 2+ uniporter (Gavin et al, 1999). Some of the mitochondrial dysfunction include altered mitochondrial respiration (Gavin et al, 1999), inhibition of mitochondrial aconitase activity (Zheng et al, 1998), loss of mitochondrial transmembrane potential (Malecki, 2001;Rao & Norenberg, 2004;Yin et al, 2008) and reduction of ATP (Milatovic et al, 2009;Roth et al, 2000). Inhibition of the mitochondrial electron transport chain by Mn (e.g.…”

Section: Manganesementioning

confidence: 99%

Systematic literature review on Parkinson's disease and Childhood Leukaemia and mode of actions for pesticides

Choi¹,

Polcher²,

Joas³

2016

EFSA Supporting Publications

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This report presents the outcomes of a systematic review (SR) identifying the mechanisms and chemicals involved in the pathogenesis of Parkinson's disease (PD) and childhood leukaemia (CL). This work serves as a basis for defining and mapping the causal linkages between a molecular initiating event (MIE) and a final adverse outcome (AO) that are relevant for the development of a prototype adverse outcome pathway (AOP) for assessing risk factors for PD and CL. Search for literature from 1990 to present was conducted using Web of Science, PubMed and TOXNET, and relevant references were selected using established inclusion/exclusion criteria and ranked using a set of quality control factors.For PD, 7,384 individual references were identified to be relevant for PD pathogenesis and chemicals associated with PD. Dopaminergic neurodegeneration in the substantia nigra leading to locomotor deficits was identified as the AO in PD. Other identified key events in PD pathogenesis include mitochondrial dysfunction, cellular accumulation of alpha-synuclein and oxidative stress. 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, rotenone and paraquat are some chemicals identified to be associated with PD pathogenesis.For CL, 1,988 individual references were identified to be relevant for CL pathogenesis and chemicals associated with CL. Chromosomal translocation, genetic damage/mutation and hyperdiploidy are considered as driving forces of CL. Except for infant leukaemia, CL pathogenesis requires a 'two-hit' model with an initiating event occurring in utero followed by a secondary hit potentially occurring after birth. Potential MIEs leading to these driving mechanisms include aberrant DNA topoisomerase II activity and erroneous DNA repair. Epigenetics appears to also play an influential role in CL pathogenesis. Benzene, bioflavonoids and organophosphates are some chemicals identified to be implicated in CL pathogenesis.The challenges of developing AOPs for these two diseases and the data gaps identified from the outcomes of this SR are also elaborated in this report. The present document has been produced and adopted by the bodies identified above as authors. This task has been carried out exclusively by the authors in the context of a contract between the European Food Safety Authority and the authors, awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors. KEY WORDSSystematic Review, Parkinson Disease, Childhood Leukaemia, Pathogenesis, Chemicals, Pesticides, Adverse Outcome Pathway SUMMARYThe aim of this project was to perform a systematic review (SR) to collect relevant publications related to the mechanisms involved in the pathogenesis of Parkinson's disease (PD)...

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Mitochondrial-dependent manganese neurotoxicity in rat primary astrocyte cultures

Cited by 117 publications

References 86 publications

Effects of Dietary Manganese on Oxidative Damage of the Neurons in Cocks

Effects of Dietary Manganese on Oxidative Damage of the Neurons in Cocks

Investigation of manganese homeostasis in dogs with anaemia and chronic enteropathy

Systematic literature review on Parkinson's disease and Childhood Leukaemia and mode of actions for pesticides

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