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Manganese basal ganglia

Callum Livingstone
Manganese (Mn) is an essential micronutrient required for the activity of metalloenzymes. It is an essential component of parenteral nutrition (PN), but requirements are low. Mn status is difficult to assess, with the commonest method being measurement of its concentration in whole blood. This method has limitations, including artifactually high concentrations resulting from contamination of specimen tubes. Mn toxicity is a well-recognized complication of PN, the risk of which increases if there is cholestasis or if the patient has received high doses...
April 1, 2017: Nutrition in Clinical Practice
R M Gorojod, A Alaimo, S Porte Alcon, F Saravia, M L Kotler
Manganese (Mn) is an essential trace metal which plays a critical role in brain physiology by acting as a cofactor for several enzymes. However, upon overexposure, Mn preferentially accumulates within the basal ganglia leading to the development of a Parkinsonism known as Manganism. Data from our group have proved that Mn induces oxidative stress-mediated apoptosis in astrocytoma C6 cells. In the present study we described how cathepsins impact on different steps of each apoptotic cascade. Evidence obtained demonstrated that Mn generates lysosomal membrane permeabilization (LMP) and cathepsin release...
April 4, 2017: Archives of Toxicology
Brad A Racette, Anat Gross, Susan R Criswell, Harvey Checkoway, Susan Searles Nielsen
Manganese (Mn) over-exposure in occupational settings is associated with basal ganglia toxicity and a movement disorder characterized by parkinsonism (i.e., the signs and symptoms of Parkinson disease). A simple test to help non-neurologists identify workers with clinical Mn neurotoxicity represents an unmet need. In a cohort of Mn-exposed workers from welding worksites, with extensive clinical data, we developed a linear regression model to predict the Unified Parkinson Disease Rating Scale motor subsection part 3 (UPDRS3) score...
March 6, 2017: Neurotoxicology
B Knauer, P Majka, K J Watkins, A W R Taylor, D Malamanova, B Paul, Hsin-Hao Yu, A I Bush, D J Hare, D H Reser
Despite the importance of transition metals for normal brain function, relatively little is known about the distribution of these elemental species across the different tissue compartments of the primate brain. In this study, we employed laser ablation-inductively coupled plasma-mass spectrometry on PFA-fixed brain sections obtained from two adult common marmosets. Concurrent cytoarchitectonic, myeloarchitectonic, and chemoarchitectonic measurements allowed for identification of the major neocortical, archaecortical, and subcortical divisions of the brain, and precise localisation of iron, manganese, and zinc concentrations within each division...
April 19, 2017: Metallomics: Integrated Biometal Science
Ying Li, Li Hong Mei, Jin Wei Qiang, Chang Xue Ji, Shuai Ju
Brain manganese deposition is led by liver dysfunction and/or portal-systemic shunting in minimal hepatic encephalopathy (MHE). Manganese is toxic and can cause cognitive disorders and extrapyramidal symptoms. Thus, reduction of manganese intake might be considered as a potential treatment strategy for MHE. In this study we aimed to investigate whether low- or no-manganese feed can improve the neuropsychological manifestations in MHE rats. Rats with MHE were established by partially ligating the portal vein and fed a manganese diet (MHE-M, 10mg per kg feed; n=24), a no-manganese diet (MHE-N; n=24) and a half-manganese diet (MHE-H; n=24) for 2, 4, 6 and 8weeks, with six rats in each subgroup...
April 7, 2017: Neuroscience
Yi Lao, Laurie-Anne Dion, Guillaume Gilbert, Maryse F Bouchard, Gabriel Rocha, Yalin Wang, Natasha Leporé, Dave Saint-Amour
Chronic manganese (Mn) exposure is associated with neuromotor and neurocognitive deficits, but the exact mechanism of Mn neurotoxicity is still unclear. With the advent of magnetic resonance imaging (MRI), in-vivo analysis of brain structures has become possible. Among different sub-cortical structures, the basal ganglia (BG) has been investigated as a putative anatomical biomarker in MR-based studies of Mn toxicity. However, previous investigations have yielded inconsistent results in terms of regional MR signal intensity changes...
February 3, 2017: Scientific Reports
Lisa G Riley, Mark J Cowley, Velimir Gayevskiy, Tony Roscioli, David R Thorburn, Kristina Prelog, Melanie Bahlo, Carolyn M Sue, Shanti Balasubramaniam, John Christodoulou
SLC39A8 variants have recently been reported to cause a type II congenital disorder of glycosylation (CDG) in patients with intellectual disability and cerebellar atrophy. Here we report a novel SLC39A8 variant in siblings with features of Leigh-like mitochondrial disease. Two sisters born to consanguineous Lebanese parents had profound developmental delay, dystonia, seizures and failure to thrive. Brain MRI of both siblings identified bilateral basal ganglia hyperintensities on T2-weighted imaging and cerebral atrophy...
December 19, 2016: Journal of Inherited Metabolic Disease
Eun-Young Lee, Paul J Eslinger, Michael R Flynn, Daymond Wagner, Guangwei Du, Mechelle M Lewis, Lan Kong, Richard B Mailman, Xuemei Huang
OBJECTIVES: Welding fumes contain several metals including manganese (Mn) and iron (Fe) that may affect the nervous system. Previous studies of potential welding-related neurotoxicity have focused primarily on Mn exposure. The current study examined neurobehavioral and brain imaging changes in asymptomatic welders and their associations with both Mn and Fe exposure measurements. METHODS: Data were obtained from subjects with (n=46) and without (controls; n=31) a history of welding exposure...
November 18, 2016: Neurotoxicology
Amal Al-Lozi, Susan Searles Nielsen, Tamara Hershey, Angela Birke, Harvey Checkoway, Susan R Criswell, Brad A Racette
BACKGROUND: Chronic exposure to manganese (Mn) is a health concern in occupations such as welding because of well-established motor effects due to basal ganglia dysfunction. We hypothesized that cognitive control (the ability to monitor, manipulate, and regulate ongoing cognitive demands) would also be affected by chronic Mn exposure. METHODS: We examined the relationship between Mn exposure and cognitive control performance in 95 workers with varying intensity and duration (median 15...
February 2017: American Journal of Industrial Medicine
Julius Juurmaa, Ricarda A L Menke, Pierre Vila, Andreas Müürsepp, Tiiu Tomberg, Pilvi Ilves, Mait Nigul, Heidi Johansen-Berg, Michael Donaghy, Charlotte J Stagg, Ainārs Stepens, Pille Taba
BACKGROUND: A permanent Parkinsonian syndrome occurs in intravenous abusers of the designer psychostimulant methcathinone (ephedrone). It is attributed to deposition of contaminant manganese, as reflected by characteristic globus pallidus hyperintensity on T1-weighted MRI. METHODS: We have investigated brain structure and function in methcathinone abusers (n = 12) compared to matched control subjects (n = 12) using T1-weighted structural and resting-state functional MRI...
November 2016: Brain and Behavior
Tanara V Peres, Maria Rosa C Schettinger, Pan Chen, Fabiano Carvalho, Daiana S Avila, Aaron B Bowman, Michael Aschner
Manganese (Mn) is an essential heavy metal. However, Mn's nutritional aspects are paralleled by its role as a neurotoxicant upon excessive exposure. In this review, we covered recent advances in identifying mechanisms of Mn uptake and its molecular actions in the brain as well as promising neuroprotective strategies. The authors focused on reporting findings regarding Mn transport mechanisms, Mn effects on cholinergic system, behavioral alterations induced by Mn exposure and studies of neuroprotective strategies against Mn intoxication...
November 4, 2016: BMC Pharmacology & Toxicology
Shao-Jun Li, Yi-Ni Luo, Yong Li, Jing-Wen Chen, Yu-Huan Mo, Zong-Xiang Yuan, Shi-Yan Ou, Chao-Yan Ou, Yue-Ming Jiang, Xiang-Fa Deng
Sodium para-aminosalicylate (PAS-Na) was first applied successfully in clinical treatment of two manganism patients with good prognosis. However, the mechanism of how PAS-Na protects against Mn-induced neurotoxicity is still elusive. The current study was conducted to explore the effects of PAS-Na on Mn-induced basal ganglia astrocyte injury, and the involvement of amino acid neurotransmitter in vitro. Basal ganglia astrocytes were exposed to 500 μM manganese chloride (MnCl2) for 24 hr, following by 50, 150, or 450 μM PAS-Na treatment for another 24 hr...
2016: Journal of Toxicological Sciences
Chao-Yan Ou, Yi-Ni Luo, Sheng-Nan He, Xiang-Fa Deng, Hai-Lan Luo, Zong-Xiang Yuan, Hao-Yang Meng, Yu-Huan Mo, Shao-Jun Li, Yue-Ming Jiang
Excessive intake of manganese (Mn) may cause neurotoxicity. Sodium para-aminosalicylic acid (PAS-Na) has been used successfully in the treatment of Mn-induced neurotoxicity. The γ-aminobutyric acid (GABA) is related with learning and memory abilities. However, the mechanism of PAS-Na on improving Mn-induced behavioral deficits is unclear. The current study was aimed to investigate the effects of PAS-Na on Mn-induced behavioral deficits and the involvement of ultrastructural alterations and γ-aminobutyric acid (GABA) metabolism in the basal ganglia of rats...
March 2017: Biological Trace Element Research
Eun-Young Lee, Michael R Flynn, Guangwei Du, Mechelle M Lewis, Amy H Herring, Eric Van Buren, Scott Van Buren, Lan Kong, Richard B Mailman, Xuemei Huang
INTRODUCTION: Welding fumes contain several metals including manganese (Mn), iron (Fe), and copper (Cu) that at high exposure may co-influence welding-related neurotoxicity. The relationship between brain accumulation of these metals and neuropathology, especially in welders with subclinical exposure levels, is unclear. This study examined the microstructural integrity of basal ganglia (BG) regions in asymptomatic welders using diffusion tensor imaging (DTI). METHODS: Subjects with (n = 43) and without (age- and gender-matched controls; n = 31) history of welding were studied...
September 2016: Toxicological Sciences: An Official Journal of the Society of Toxicology
Mechelle M Lewis, Eun-Young Lee, Hang Jin Jo, Guangwei Du, Jaebum Park, Michael R Flynn, Lan Kong, Mark L Latash, Xuemei Huang
BACKGROUND: Multi-digit synergies, a recently developed, theory-based method to quantify stability of motor action, are shown to reflect basal ganglia dysfunction associated with parkinsonian syndromes. In this study, we tested the hypothesis that multi-digit synergies may capture early and subclinical basal ganglia dysfunction. We chose asymptomatic welders to test the hypothesis because the basal ganglia are known to be most susceptible to neurotoxicity caused by welding-related metal accumulation (such as manganese and iron)...
June 30, 2016: Neurotoxicology
Khairunnisa Mukhtiar, Shahnaz Ibrahim, Karin Tuschl, Phillipa Mills
Manganese (Mn) is an essential element for metabolic pathways but it can be toxic when present in excessive amounts in the body. Hypermanganesemia along with dystonia, polycythemia, characteristic MRI brain findings in the basal ganglia, and chronic liver disease are the hallmarks of an inherited Mn transporter defect due to mutations in the SLC30A10 gene. We are reporting three siblings who presented with features of dystonia, polycythemia, MRI brain showing basal ganglia hyperintensity on T1 weighted images and chronic liver disease...
October 2016: Brain & Development
Dong-Suk Kim, Huajun Jin, Vellareddy Anantharam, Richard Gordon, Arthi Kanthasamy, Anumantha G Kanthasamy
Chronic exposure to elevated levels of manganese (Mn) has been linked to a Parkinsonian-like movement disorder, resulting from dysfunction of the extrapyramidal motor system within the basal ganglia. However, the exact cellular and molecular mechanisms of Mn-induced neurotoxicity remain elusive. In this study, we treated C57BL/6J mice with 30mg/kg Mn via oral gavage for 30 days. Interestingly, in nigral tissues of Mn-exposed mice, we found a significant downregulation of the truncated isoform of p73 protein at the N-terminus (ΔNp73)...
March 2017: Neurotoxicology
Lin Tian, Kiao Inthavong, Göran Lidén, Yidan Shang, Jiyuan Tu
Welding fume is a complex mixture containing ultra-fine particles in the nanometer range. Rather than being in the form of a singular sphere, due to the high particle concentration, welding fume particles agglomerate into long straight chains, branches, or other forms of compact shapes. Understanding the transport and deposition of these nano-agglomerates in human respiratory systems is of great interest as welding fumes are a known health hazard. The neurotoxin manganese (Mn) is a common element in welding fumes...
July 2016: Annals of Occupational Hygiene
Safa Bouabid, Anass Tinakoua, Nouria Lakhdar-Ghazal, Abdelhamid Benazzouz
Manganese (Mn) is an essential element required for many physiological functions. While it is essential at physiological levels, excessive accumulation of Mn in the brain causes severe dysfunctions in the central nervous system known as manganism. Manganism is an extrapyramidal disorder characterized by motor disturbances associated with neuropsychiatric and cognitive disabilities similar to Parkinsonism. As the primary brain regions targeted by Mn are the basal ganglia, known to be involved in the pathophysiology of extrapyramidal disorders, this review will examine the impact of Mn exposure on the basal ganglia circuitry and neurotransmitters in relation to motor and non-motor disorders...
November 26, 2015: Journal of Neurochemistry
David Dorman
The central nervous system's extrapyramidal system provides involuntary motor control to the muscles of the head, neck, and limbs. Toxicants that affect the extrapyramidal system are generally clinically characterized by impaired motor control, which is usually the result of basal ganglionic dysfunction. A variety of extrapyramidal syndromes are recognized in humans and include Parkinson's disease, secondary parkinsonism, other degenerative diseases of the basal ganglia, and clinical syndromes that result in dystonia, dyskinesia, essential tremor, and other forms of tremor and chorea...
2015: Handbook of Clinical Neurology
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