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Manganese basal ganglia

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...
August 5, 2016: 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 C57/BL6J 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)...
April 20, 2016: 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
Judy L Aschner, Adam Anderson, James Christopher Slaughter, Michael Aschner, Steven Steele, Amy Beller, Amanda Mouvery, Heather M Furlong, Nathalie L Maitre
BACKGROUND: Manganese, an essential metal for normal growth and development, is neurotoxic on excessive exposure. Standard trace element-supplemented neonatal parenteral nutrition (PN) has a high manganese content and bypasses normal gastrointestinal absorptive control mechanisms, which places infants at risk of manganese neurotoxicity. Magnetic resonance (MR) relaxometry demonstrating short T1 relaxation time (T1R) in the basal ganglia reflects excessive brain manganese accumulation...
December 2015: American Journal of Clinical Nutrition
Noam Gordon, Gadi Goelman
The monoamine-deficiency and the hippocampal-neurogenesis hypotheses of depression propose that alterations in the serotonin system and of hippocampal functionality are critical in the pathogenesis of depression. We measured the alterations in the connectivity level of the raphe nucleus in the chronic mild stress (CMS) rat model of depression using the manganese enhanced MRI method (MEMRI). Manganese ions were injected into the median raphe and their anterograde intracellular propagation was followed. Depression-like behavior was demonstrated using the sucrose preference tests...
January 1, 2016: Behavioural Brain Research
Shao-Jun Li, Yong Li, Jing-Wen Chen, Zong-Xiang Yuan, Yu-Huan Mo, Guo-Dong Lu, Yue-Ming Jiang, Chao-Yan Ou, Fang Wang, Xiao-Wei Huang, Yi-Ni Luo, Shi-Yan Ou, Yan-Ni Huang
Manganese (Mn), an essential trace metal for protein synthesis and particularly neurotransmitter metabolism, preferentially accumulates in basal ganglia. However, excessive Mn accumulation may cause neurotoxicity referred to as manganism. Sodium para-aminosalicylic acid (PAS-Na) has been used to treat manganism with unclear molecular mechanisms. Thus, we aim to explore whether PAS-Na can inhibit Mn-induced neuronal injury in basal ganglia in vitro. We exposed basal ganglia neurons with 50 μM manganese chloride (MnCl2) for 24 h and then replaced with 50, 150, and 450 μM PAS-Na treatment for another 24 h...
April 2016: Biological Trace Element Research
Tomás R Guilarte, Kalynda K Gonzales
Movement abnormalities caused by chronic manganese (Mn) intoxication clinically resemble but are not identical to those in idiopathic Parkinson's disease. In fact, the most successful parkinsonian drug treatment, the dopamine precursor levodopa, is ineffective in alleviating Mn-induced motor symptoms, implying that parkinsonism in Mn-exposed individuals may not be linked to midbrain dopaminergic neuron cell loss. Over the last decade, supporting evidence from human and nonhuman primates has emerged that Mn-induced parkinsonism partially results from damage to basal ganglia nuclei of the striatal "direct pathway" (ie, the caudate/putamen, internal globus pallidus, and substantia nigra pars reticulata) and a marked inhibition of striatal dopamine release in the absence of nigrostriatal dopamine terminal degeneration...
August 2015: Toxicological Sciences: An Official Journal of the Society of Toxicology
Tanara V Peres, Helena Eyng, Samantha C Lopes, Dirleise Colle, Filipe M Gonçalves, Débora K R Venske, Mark W Lopes, Juliana Ben, Julia Bornhorst, Tanja Schwerdtle, Michael Aschner, Marcelo Farina, Rui D Prediger, Rodrigo B Leal
Exposure to high manganese (Mn) levels may damage the basal ganglia, leading to a syndrome analogous to Parkinson's disease, with motor and cognitive impairments. The molecular mechanisms underlying Mn neurotoxicity, particularly during development, still deserve further investigation. Herein, we addressed whether early-life Mn exposure affects motor coordination and cognitive function in adulthood and potential underlying mechanisms. Male Wistar rats were exposed intraperitoneally to saline (control) or MnCl2 (5, 10 or 20 mg/kg/day) from post-natal day (PND) 8-12...
September 2015: Neurotoxicology
Gunnar F Kwakye, Monica M B Paoliello, Somshuvra Mukhopadhyay, Aaron B Bowman, Michael Aschner
Manganese (Mn) is an essential trace element necessary for physiological processes that support development, growth and neuronal function. Secondary to elevated exposure or decreased excretion, Mn accumulates in the basal ganglia region of the brain and may cause a parkinsonian-like syndrome, referred to as manganism. The present review discusses the advances made in understanding the essentiality and neurotoxicity of Mn. We review occupational Mn-induced parkinsonism and the dynamic modes of Mn transport in biological systems, as well as the detection and pharmacokinetic modeling of Mn trafficking...
July 6, 2015: International Journal of Environmental Research and Public Health
Susan R Criswell, Gill Nelson, Luis F Gonzalez-Cuyar, John Huang, Joshua S Shimony, Harvey Checkoway, Christopher D Simpson, Russell Dills, Noah S Seixas, Brad A Racette
BACKGROUND: Manganese (Mn) exposure is associated with increased T1-weighted magnetic resonance imaging (MRI) signal in the basal ganglia. T1 signal intensity has been correlated with occupational Mn exposure but not with clinical symptomatology or neuropathology. OBJECTIVES: This study investigated predictors of ex vivo T1 MRI basal ganglia signal intensity in neuropathologic tissue obtained from deceased South African mine workers. METHODS: A 3...
July 2015: Neurotoxicology
Anna Dolgan, Slawomir Budrewicz, Magdalena Koszewicz, Joanna Bladowska, Krzysztof Slotwinski, Mieszko Zagrajek, Ewa Koziorowska-Gawron, Ryszard Podemski
OBJECTIVES: A new form of manganese poisoning is related to the intravenous use of self-prepared methcathinone hydrochloride (ephedrone). Manganese encephalopathy typically manifests as a levodopa-resistant parkinsonism. MAIN POINTS: A 32-year-old drug-addicted man with acute gait disturbances after the ephedrone injections was presented. Choreic movements, severe postural instability, and "cock-walk" gait were observed. Magnetic resonance imaging T1 images showed high signal intensity of white matter in the basal ganglia and pituitary gland, and T2 images showed decreased signal mostly of globus pallidus with decreased N-acetylaspartate and choline levels in MR spectroscopy...
May 2015: Journal of Addiction Medicine
Kevin K Kumar, Cody R Goodwin, Michael A Uhouse, Julia Bornhorst, Tanja Schwerdtle, Michael Aschner, John A McLean, Aaron B Bowman
Manganese (Mn) is an essential micronutrient for development and function of the nervous system. Deficiencies in Mn transport have been implicated in the pathogenesis of Huntington's disease (HD), an autosomal dominant neurodegenerative disorder characterized by loss of medium spiny neurons of the striatum. Brain Mn levels are highest in striatum and other basal ganglia structures, the most sensitive brain regions to Mn neurotoxicity. Mouse models of HD exhibit decreased striatal Mn accumulation and HD striatal neuron models are resistant to Mn cytotoxicity...
February 2015: Metallomics: Integrated Biometal Science
Andrew M Tidball, Miles R Bryan, Michael A Uhouse, Kevin K Kumar, Asad A Aboud, Jack E Feist, Kevin C Ess, M Diana Neely, Michael Aschner, Aaron B Bowman
The essential micronutrient manganese is enriched in brain, especially in the basal ganglia. We sought to identify neuronal signaling pathways responsive to neurologically relevant manganese levels, as previous data suggested that alterations in striatal manganese handling occur in Huntington's disease (HD) models. We found that p53 phosphorylation at serine 15 is the most responsive cell signaling event to manganese exposure (of 18 tested) in human neuroprogenitors and a mouse striatal cell line. Manganese-dependent activation of p53 was severely diminished in HD cells...
April 1, 2015: Human Molecular Genetics
Marissa G Baker, Susan R Criswell, Brad A Racette, Christopher D Simpson, Lianne Sheppard, Harvey Checkoway, Noah S Seixas
OBJECTIVE: Long-term, high-level exposure to manganese (Mn) is associated with impaired central nervous system (CNS) function. We quantitatively explored relations between low-level Mn exposure and selected neurological outcomes in a longitudinal inception cohort of asymptomatic welder trainees. METHODS: Welders with no previous occupational Mn exposure were observed approximately every three months over the course of the five-quarter traineeship. Fifty-six welders were assessed for motor function using the Unified Parkinson Disease Rating Scale motor subsection part 3 (UPDRS3) and Grooved Pegboard tests...
January 2015: Scandinavian Journal of Work, Environment & Health
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