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Keith M. Erikson

** Education - Research Fellow, Wake Forest University. School of Medicine, 2001-2003 - Ph.D., The Pennsylvania State University, 2000 **Research Interest: Effects of abnormal trace element (iron, manganese) metabolism on neurobiological and neurochemical outcomes, using animal models and cell culture.

There are 56 included publications by Keith M. Erikson :

TitleDateViewsBrief Description
Airborne manganese exposure differentially affects end points of oxidative stress in an age- and sex-dependent manner 2004 317 Juvenile female and male (young) and 16-mo-old male (old) rats inhaled manganese in the form of manganese sulfate (MnSO4) at 0, 0.01, 0.1, and 0.5 mg Mn/m3 or manganese phosphate at 0.1 mg Mn/m3 in exposures of 6 h/d, 5 d/wk for 13 wk. We assessed bi...
Alterations of oxidative stress biomarkers due to In utero and neonatal exposures of airborne manganese 2006 300 Neonatal rats were exposed to airborne manganese sulfate (MnSO4) (0, 0.05, 0.5, or 1.0 mg Mn/m3) during gestation (d 0–19) and postnatal days (PNDs) 1–18. On PND 19, rats were killed, and we assessed biochemical end points indicative of oxidative str...
Altered manganese homeostasis and manganese toxicity in Huntington’s Disease striatal cell model are not due to defects in iron transport system. 2010 106 Expansion of a polyglutamine tract in Huntingtin (Htt) leads to the degeneration of medium spiny neurons in Huntington's disease (HD). Furthermore, the HTT gene has been functionally linked to iron (Fe) metabolism, and HD patients show alterations in...
Basal Ganglia Intensity Indices and Diffusion Weighted Imaging in Manganese Exposed Welders. 2012 95 Objectives Manganese exposure leads to diffuse cerebral metal deposition with the highest concentration in the globus pallidus associated with increased T1-weighted MRI signal. T1 signal intensity in extra-pallidal basal ganglia (caudate and putamen)...
Brain Accumulation of depleted uranium in rats following 3 or 6 month treatment with implanted depleted uranium pellets 2006 276 Depleted uranium (DU) is used to reinforce armor shielding and increase penetrability of military munitions. Although the data are conflicting, DU has been invoked as a potential etiological factor in Gulf War syndrome. We examined regional brain DU ...
Brain Manganese Accumulation is Inversely Related to GABA Uptake in Male and Female Rats 2007 281 Iron (Fe) is an essential trace metal involved in numerous cellular processes. Iron deficiency (ID) is reported as the most prevalent nutritional problem worldwide. Increasing evidence suggests that ID is associated with altered neurotransmitter meta...
Changes in Dietary Iron Exacerbate Regional Brain Manganese Accumulation as Determined by Magnetic Resonance Imaging (MRI). 2011 78 Manganese (Mn) is an essential metal required for normal homeostasis. Humans chronically exposed to high Mn levels, however, may exhibit psychomotor signs secondary to increased brain Mn. As Mn and iron (Fe) share several cellular membrane transporte...
Depleted uranium is not toxic to rat brain endothelial (RBE4) cells 2006 385 Studies on Gulf War veterans with depleted uranium (DU) fragments embedded in their soft tissues have led to suggestions of possible DU-induced neurotoxicity. We investigated DU uptake into cultured rat brain endothelial cells (RBE4). Following the d...
Disease-toxicant screen reveals a nueroprotective interaction between Huntington’s disease and manganese exposure 2009 536 Recognizing the similarities between Huntington’s disease (HD) pathophysiology and the neurotoxicology of various metals, we hypothesized that they may exhibit disease-toxicant interactions revealing cellular pathways underlying neurodegeneration. He...
Distribution of brain iron, ferritin and transferrin in the 28 day old piglet 1998 601 This study sought to gain understanding of the effect of iron deficiency anemia on regional brain iron, ferritin, and transferrin concentrations in the growing piglet. We wanted to use an animal whose development is more similar to human development ...
Duration of airborne-manganese exposure in rhesus monkeys is associated with brain regional changes in biomarkers of neurotoxicity 2008 267 Juvenile (20–24-month-old) rhesus monkeys were exposed to airborne-manganese sulfate (MnSO4) 1.5 mg Mn/m3 (6 h/day, 5 days/week) for 15 or 33 days, or for 65 days followed by a 45 or 90 days post-exposure recovery period, or air. We assessed biochemi...
Effects of Inhaled Manganese on Biomarkers of Oxidative Stress in the Rat Brain 2006 515 Manganese (Mn) is a ubiquitous and essential element that can be toxic at high doses. In individuals exposed to high levels of this metal, Mn can accumulate in various brain regions, leading to neurotoxicity. In particular, Mn accumulation in the mid...
Effects of Manganese on the developing rat brain: oxidative-stress related endpoints 2002 413 We evaluated biochemical endpoints related to oxidative stress in brains of neonatal rats exposed to manganese (Mn). Oral Mn chloride (MnCl2) (0, 25, or 50 mg Mn chloride kg-1 body weight per day) was given daily to neonatal rats throughout lactation...
The effects of manganese on glutamate, dopamine and -y-aminobutyric acid regulation 2006 578 Exposure to high levels of manganese (Mn) results in a neurological disorder, termed manganism, which shares a similar phenotype to Parkinson’s disease due to the involvement of the basal ganglia circuitry in both. The initial symptoms of manganism a...
Extracellular Norepinephrine, Norepinephrine Receptor and Transporter Protein and mRNA Levels Are Differentially Altered in the Developing Rat Brain Due to Dietary Iron Deficiency and Manganese Exposure 2009 349 Manganese (Mn) is an essential trace element, but overexposure is characterized by Parkinson's like symptoms in extreme cases. Previous studies have shown that Mn accumulation is exacerbated by dietary iron deficiency (ID) and disturbances in norepin...
Ferroportin is a manganese responsive protein that decreases manganese cytotoxicity and accumulation 2009 2405 Although manganese (Mn) is an essential trace element for human development and growth, chronic exposure to excessive Mn levels can result in psychiatric and motor disturbances, referred to as manganism. However, there are no known mechanism(s) for e...
Functional coding variation in recombinant inbred mouse lines reveals multiple serotonin transporter-associated phenotypes 2009 268 The human serotonin (5-hydroxytryptamine, 5-HT) transporter (hSERT, SLC6A4) figures prominently in the etiology and treatment of many prevalent neurobehavioral disorders including anxiety, alcoholism, depression, autism, and obsessive-compulsive dis...
Genetic differences in hepatic lipid peroxidation potential and iron levels in mice 2002 408 Oxidative damage to macromolecules, including lipids, has been hypothesized as a mechanism of aging. One end product of lipid peroxidation, malondialdehyde (MDA), is often quantified as a measure of oxidative damage to lipids. We used a commercial co...
Genetic risk for Parkinson's disease correlates with alterations in neuronal manganese sensitivity between two human subjects. 2012 122 Manganese (Mn) is an environmental risk factor for Parkinson's disease (PD). Recessive inheritance of PARK2 mutations is strongly associated with early onset PD (EOPD). It is widely assumed that the influence of PD environmental risk factors may be e...
Globus Pallidus: A target brain region for divalent metal accumulation due to dietary iron deficiency 2004 438 Recently, iron deficiency has been connected with a heterogeneous accumulation of manganese in the rat brain. The striatum is particularly vulnerable, for there is a significant negative correlation between accumulated manganese and y-aminobutyric ac...
Glutamate/aspartate transporter (GLAST), taurine transporter and metallothionein mRNA levels are differentially altered in astrocytes exposed to manganese chloride, manganese phosphate or manganese sulfate 2002 328 Manganese (Mn)-induced neurotoxicity can occur due to environmental exposure (air pollution, soil, water) and/or metabolic aberrations (decreased biliary excretion). High brain manganese levels lead to oxidative stress, as well as alterations in neur...
In vivo dopamine metabolism in iron deficiency anemia 1997 679 Previous studies of dopamine metabolism in iron-deficient rats demonstrated an elevation in extra-neuronal levels of dopamine and a depression in the number of dopamine D2 receptors; however, the importance of anemia per se and the reversibility of t...
In vivo manganese exposure modulates ERK, AKT and DARPP-32 in the Striatum of Developing Rats, and Impairs their Motor Function. 2012 75 Manganese (Mn) is an essential metal for development and metabolism. However, exposures to high Mn levels may be toxic, especially to the central nervous system (CNS). Neurotoxicity is commonly due to occupational or environmental exposures leading t...
Increased manganese uptake by primary astrocyte cultures with altered iron status is mediated primarily by divalent metal transporter 2006 413 Neurotoxicity due to excessive brain manganese (Mn) accumulation can occur via occupational exposure to aerosols or dusts that contain extremely high levels (> 1–5 mg Mn/m3) of Mn, or metabolic aberrations (decreased biliary excretion). Given the put...
Inhibition of DAT function attenuates manganese accumulation in the globus pallidus 2007 277 Manganese (Mn) is an essential nutrient, though exposure to high concentrations may result in neurotoxicity characterized by alterations in dopamine neurobiology. To date, it remains elusive how and why Mn targets dopaminergic neurons although recent...
Interactions between excessive manganese-exposure and dietary iron-deficiency in neurodegeneration 2005 516 For nearly a century, manganese has been recognized as an essential nutrient for proper bone formation, lipid, amino acid and carbohydrate metabolism. While manganese deficiency is characterized by symptoms ranging from stunted growth and poor bone r...
Iron deficiency alters dopamine transporter functioning in rat striatum 2000 361 Iron deficiency anemia In early life produces profound changes in both in vivo and In vitro evaluations of dopamine (DA) functioning. This study employed both behavioral and biochemical approaches to examine the biological bases of alterations in str...
Iron Deficiency Decreases dopamine D1 and D2 receptors in rat brain 2001 1012 Iron deficiency (ID) in early life is known to alter neurological development and functioning, but data regarding specific effects on dopamine biology are lacking. The objective of this study was to determine the extent of functional alterations in d...
Iron Deficiency in Young Rats Alters the Distribution of Vitamin A between Plasma and Liver and between Hepatic Retinol and Retinyl Esters 1999 305 We assessed whether iron deficiency alters the concentration of vitamin A (VA) in plasma or liver and the chemical distribution between hepatic unesterified and esterified retinol. Weanling male Sprague-Dawley rats (n = 10/group) were allocate...
Iron overload alters iron-regulatory genes and proteins, down-regulates osteoblastic phenotype, and is associated with apoptosis in fetal rat calvaria cultures 2009 591 Iron overload has been implicated in decreased bone mineral density. However, the effect of iron overload on osteoblast lineage cells remains poorly understood. The purpose of this study was to examine osteoblast differentiation, function, and apopto...
Leaching of trace elements from biological tissue by formalin fixation 2008 588 In studies of trace elements in biological tissue, it is imperative that sample handling does not substantially change element concentrations. In many cases, fresh tissue is not available for study, but formalin-fixed tissue is. Formalin fixation has...
Manganese accumulates in iron deficient rat brain regions in a heterogeneous fashion and is associated with neurochemical alterations 2002 371 Previous studies have shown that iron deficiency (ID) increases brain manganese (Mn), but specific regional changes have not been addressed. Weanling rats were fed one of three semipurified diets: control (CN), iron deficient (ID), or iron deficient/...
Manganese Accumulation in Membrane Fractions of Primary Astrocytes is Associated with Decreased ?-Aminobutyric Acid (GABA) Uptake, and is Exacerbated by Oleic Acid and Palmitate 2014 12 Manganese (Mn) exposure interferes with GABA uptake; however, the effects of Mn on GABA transport proteins (GATs) have not been identified. We sought to characterize how Mn impairs GAT function in primary rat astrocytes. Astrocytes exposed to Mn (500...
Manganese and its Role in Parkinson's disease: from Transport to Neuropathology. 2009 407 The purpose of this review is to highlight recent advances in the neuropathology associated with Mn exposures. We commence with a discussion on occupational manganism and clinical aspects of the disorder. This is followed by novel considerations on M...
Manganese causes differential regulation of glutamate transporter (GLAST), taurine transporter, and metallothionein in cultured rat astrocytes 2002 434 Neurotoxicity due to excessive brain manganese (Mn) can occur due to environmental (air pollution, soil, water) and/ or metabolic aberrations (decreased biliary excretion). Manganese is associated with oxidative stress, as well as alterations in neur...
Manganese Dosimetry: Species Differences and Implications for Neurotoxicity 2005 1810 Manganese (Mn) is an essential mineral that is found at low levels in food, water, and the air. Under certain high-dose exposure conditions, elevations in tissue manganese levels can occur. Excessive manganese accumulation can result in adverse neuro...
Manganese exposure alters extracellular GABA, GABA receptor and transporter protein and mRNA levels in the developing rat brain 2008 473 Unlike other essential trace elements (e.g., zinc and iron) it is the toxicity of manganese (Mn) that is more common in human populations than its deficiency. Data suggest alterations in dopamine biology may drive the effects associated with Mn neuro...
Manganese Exposure and Induced Oxidative Stress in the Rat Brain 2004 846 Neurotoxicity linked to excessive brain manganese levels can occur as a result of high level Mn exposures and/or metabolic aberrations (liver disease and decreased biliary excretion). Increased brain manganese levels have been reported to induce oxid...
Manganese Exposure Inhibits the Clearance of Extracellular GABA and Influences Taurine Homeostasis in the Striatum of Developing Rats 2010 176 Manganese (Mn) accumulation in the brain has been shown to alter the neurochemistry of the basal ganglia. Mn-induced alterations in dopamine biology are fairly well understood, but recently more evidence has emerged characterizing the role of ?-amino...
Manganese Inhalation by Rhesus Monkeys is Associated with Brain Regional Changes in Biomarkers of Neurotoxicity 2007 249 The purpose of this study was to evaluate biochemical markers of neurotoxicity following subchronic manganese sulfate (MnSO4) inhalation. Juvenile rhesus monkeys were exposed to MnSO4 at 0, 0.06, 0.3, or 1.5 mg Mn/m3 for 65 days. Glutamine synthetase...
Manganese Neurotoxicity 2004 1507 Manganese is an essential trace element and it is required for many ubiquitous enzymatic reactions. While manganese deficiency rarely occurs in humans, manganese toxicity is known to occur in certain occupational settings through inhalation of mangan...
Manganese neurotoxicity and GABA/glutamate interactions 2003 461 Brain extracellular concentrations of amino acids (e.g. aspartate, glutamate, taurine) and divalent metals (e.g. zinc, copper, manganese) are primarily regulated by astrocytes. Adequate glutamate homeostasis is essential for the normal functioning of...
Manganese Neurotoxicity: A Focus on the Neonate 2007 409 Manganese (Mn) is an essential trace metal found in all tissues, and it is required for normal amino acid, lipid, protein, and carbohydrate metabolism. While Mn deficiency is extremely rare in humans, toxicity due to overexposure of Mn is more preval...
Manganese-exposed developing rats display motor deficits and striatal oxidative stress that are reversed by Trolox 2013 103 While manganese (Mn) is essential for proper central nervous system (CNS) development, excessive Mn exposure may lead to neurotoxicity. Mn preferentially accumulates in the basal ganglia, and in adults it may cause Parkinson’s disease–like disorder. ...
Measuring Brain Manganese and Iron Accumulation in Rats Following 14-weeks of Low-Dose Manganese Treatment Using Atomic Absorption Spectroscopy (AAS) and Magnetic Resonance Imaging (MRI) 2008 452 Chronic exposure to manganese (Mn) may lead to a movement disorder due to preferential Mn accumulation in the globus pallidus and other basal ganglia nuclei. Iron (Fe) deficiency also results in increased brain Mn levels, as well as dysregulation of ...
A Model for the Analysis of Competitive Relaxation Effects of Manganese and Iron in Vivo 2009 581 Manganese (Mn) and iron (Fe) are both paramagnetic species that can affect magnetic resonance relaxation rates. They also share common transport systems in vivo and thus in experimental models of metal exposure their effects on relaxation rates may i...
Neonatal iron deficiency results in irreversible changes in dopamine metabolism in the rat 2003 293 Iron deficiency in human infants and in young animal models produces changes in neural functioning that may be related to monoamine metabolism. This study employed both behavioral and biochemical approaches in a design using cross-fostering to examin...
Neurobehavioral analysis of developmental iron deficiency in rats 2002 470 Iron deficiency (ID) in early life alters the course of behavioral and cognitive development in humans, causing decreased physical activity and responsiveness to the environment. The effects of ID on behavior are similar in rats and hypothesized to b...
Obesity Alters Adipose Tissue Macrophage Iron Content and Tissue Iron Distribution 2014 20 Adipose tissue (AT) expansion is accompanied by the infiltration and accumulation of AT macrophages (ATMs), as well as a shift in ATM polarization. Several studies have implicated recruited M1 ATMs in the metabolic consequences of obesity; however, l...
Organotellurium and Organoselenium compounds attenuate Mn-induced toxicity in C. elegans by preventing oxidative stress. 2012 493 Organochalcogens have been widely studied given their antioxidant activity, which confers neuroprotection, antiulcer, and antidiabetic properties. Given the complexity of mammalian models, understanding the cellular and molecular effects of organocha...
Oxidative Stress is Induced in the Rat Brain Following Repeated Inhalation Exposure to Manganese Sulfate 2003 423 Eight-week-old rats inhaled manganese (Mn) in the form of MnSO4 at 0, 0.03, 0.3, or 3.0 mg Mn/m3 for 6 h/d for 7 d/wk (14 consecutive exposures). Brain manganese concentrations in these animals were reported by Dorman et al. in 2001, noting the follo...
Persistent alterations in biomarkers of oxidative stress due to combined in utero and neonatal manganese inhalation 2005 267 Neonatal female and male rats were exposed to airborne manganese sulfate (MnSO4) during gestation and postnatal d 1–18. Three weeks post-exposure, rats were killed and we assessed biochemical end points indica-tive of oxidative stress in five brain r...
Regional brain iron, ferritin and transferrin concentrations during iron deficiency and iron repletion in developing rats 1997 646 Iron deficiency in young rats leads to a decrease In brain iron and ferritin concentrations, an increase in transferrin (Tf) concentration, and an increased rate of uptake of iron from the plasma pool. We conducted two experiments to determine whethe...
SMF-1, SMF-2, SMF-3 DMT-1 orthologues regulate and are regulated differentially by manganese levels in C. Elegans 2009 1548 Manganese (Mn) is an essential metal that can exert toxic effects at high concentrations, eventually leading to Parkinsonism. A major transporter of Mn in mammals is the divalent-metal transporter (DMT1). We characterize here DMT1-like proteins in th...
The uptake of manganese in brain endothelial cultures 2002 281 The present study focused on central nervous system (CNS) transport kinetics of manganese phosphate and manganese sulfate; these findings were correlated with the transport kinetics of manganese chloride (MnCl2), a model Mn compound that has been pr...
Waterborne Manganese Exposure Alters Plasma, Brain, and Liver Metabolites Accompanied by Changes in Stereotypic Behaviors 2012 338 Overexposure to waterborne manganese (Mn) is linked with cognitive impairment in children and neurochemical abnormalities in other experimental models. In order to characterize the threshold between Mn-exposure and altered neurochemistry, it is impor...