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https://www.readbyqxmd.com/read/28400118/pre-clinical-therapeutic-development-of-a-series-of-metalloporphyrins-for-parkinson-s-disease
#1
Li-Ping Liang, Jie Huang, Ruth Fulton, Jennifer N Pearson-Smith, Brian J Day, Manisha Patel
Reactive oxygen species are a well-defined therapeutic target for Parkinson's disease (PD) and pharmacological agents that catalytically scavenge reactive species are promising neuroprotective strategies for treatment. Metalloporphyrins are synthetic catalytic antioxidants that mimic the body's own antioxidant enzymes i.e. superoxide dismutases and catalase. The goal of this study was to determine if newly designed metalloporphyrins have enhanced pharmacodynamics including oral bioavailability, longer plasma elimination half-lives, penetrate the blood brain barrier, and show promise for PD treatment...
April 8, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28391012/mapping-of-pain-circuitry-in-early-post-natal-development-using-manganese-enhanced-mri-in-rats
#2
M M Sperry, B M Kandel, S Wehrli, K N Bass, S R Das, P S Dhillon, J C Gee, G A Barr
Premature or ill full-term infants are subject to a number of noxious procedures as part of their necessary medical care. Although we know that human infants show neural changes in response to such procedures, we know little of the sensory or affective brain circuitry activated by pain. In rodent models, the focus has been on spinal cord and, more recently, midbrain and medulla. The present study assesses activation of brain circuits using manganese-enhanced magnetic resonance imaging (MEMRI). Uptake of manganese, a paramagnetic contrast agent that is transported across active synapses and along axons, was measured in response to a hindpaw injection of dilute formalin in 12-day-old rat pups, the age at which rats begin to show aversion learning and which is roughly the equivalent of full-term human infants...
April 5, 2017: Neuroscience
https://www.readbyqxmd.com/read/28378122/interplay-between-lysosomal-mitochondrial-and-death-receptor-pathways-during-manganese-induced-apoptosis-in-glial-cells
#3
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
https://www.readbyqxmd.com/read/28366802/in-vivo-epr-pharmacokinetic-evaluation-of-the-redox-status-and-the-blood-brain-barrier-permeability-in-the-sod1-g93a-als-rat-model
#4
Stefan Stamenković, Aleksandra Pavićević, Miloš Mojović, Ana Popović-Bijelić, Vesna Selaković, Pavle Andjus, Goran Bačić
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder affecting the motor pathways of the central nervous system. Although a number of pathophysiological mechanisms have been described in the disease, post mortem and animal model studies indicate blood-brain barrier (BBB) disruption and elevated production of reactive oxygen species as major contributors to disease pathology. In this study, the BBB permeability and the brain tissue redox status of the SOD1(G93A) ALS rat model in the presymptomatic (preALS) and symptomatic (ALS) stages of the disease were investigated by in vivo EPR spectroscopy using three aminoxyl radicals with different cell membrane and BBB permeabilities, Tempol, 3-carbamoyl proxyl (3CP), and 3-carboxy proxyl (3CxP)...
March 31, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28366719/minocycline-restores-cognitive-relative-altered-proteins-in-young-bile-duct-ligated-rat-prefrontal-cortex
#5
Shih-Wen Li, Yu-Chieh Chen, Jiunn-Ming Sheen, Mei-Hsin Hsu, You-Lin Tain, Kow-Aung Chang, Li-Tung Huang
AIMS: Bile duct ligation (BDL) is used as an animal model for hepatic encephalopathy (HE) accompanied by cognitive impairment. Through a proteomic analysis approach, we sought to identify affected proteins that are involved in cognition, by analyzing the prefrontal cortex of young BDL rats and testing the effects of minocycline on the affected rats. MAIN METHODS: Young BDL rats were induced at postnatal day 17. Minocycline was administered through a slow release pellet implanted into their peritoneum...
March 30, 2017: Life Sciences
https://www.readbyqxmd.com/read/28337287/memri-is-a-biomarker-defining-nicotine-specific-neuronal-responses-in-subregions-of-the-rodent-brain
#6
Aditya N Bade, Howard E Gendelman, Michael D Boska, Yutong Liu
Nicotine dependence is defined by dopaminergic neuronal activation within the nucleus accumbens (ACB) and by affected neural projections from nicotine-stimulated neurons. Control of any subsequent neural activities would underpin any smoking cessation strategy. While extensive efforts have been made to study the pathophysiology of nicotine addiction, more limited works were developed to find imaging biomarkers. If such biomarkers are made available, addictive behaviors could be monitored noninvasively. To such ends, we employed manganese (Mn(2+))-enhanced magnetic resonance imaging (MEMRI) to determine whether it could be used to monitor neuronal activities after acute and chronic nicotine exposure in rats...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28331914/effects-and-mechanisms-of-a-new-multivitamin-on-chronic-metabolic-syndromes-and-aging
#7
Su-Xi Wu, Xuewei Jiang, Yu-Ying Liu, Lin-Feng Chen, Jun Tao
BACKGROUND: Increased occurrence of chronic syndromes has prompted researchers to investigate and develop drugs and methods for controlling chronic syndromes with a view to improve human health and reduce early aging. MATERIAL AND METHODS: Human trials: After the allotted multivitamin pills or placebo pills had been taken for a stipulated period of about 2 months, the volunteers filled out feedback forms on curative effects of the pills in line with the health examination reports...
2017: African Journal of Traditional, Complementary, and Alternative Medicines: AJTCAM
https://www.readbyqxmd.com/read/28306727/biodistribution-and-pet-imaging-of-pharmacokinetics-of-manganese-in-mice-using-manganese-52
#8
A Lake Wooten, Tolulope A Aweda, Benjamin C Lewis, Rebecca B Gross, Suzanne E Lapi
Manganese is essential to life, and humans typically absorb sufficient quantities of this element from a normal healthy diet; however, chronic, elevated ingestion or inhalation of manganese can be neurotoxic, potentially leading to manganism. Although imaging of large amounts of accumulated Mn(II) is possible by MRI, quantitative measurement of the biodistribution of manganese, particularly at the trace level, can be challenging. In this study, we produced the positron-emitting radionuclide 52Mn (t1/2 = 5.6 d) by proton bombardment (Ep<15 MeV) of chromium metal, followed by solid-phase isolation by cation-exchange chromatography...
2017: PloS One
https://www.readbyqxmd.com/read/28284465/neurological-disorders-in-liver-transplant-candidates-pathophysiology-and-clinical-assessment
#9
REVIEW
Paolo Feltracco, Annachiara Cagnin, Cristiana Carollo, Stefania Barbieri, Carlo Ori
Compromised liver function, as a consequence of acute liver insufficiency or severe chronic liver disease may be associated with various neurological syndromes, which involve both central and peripheral nervous system. Acute and severe hyperammoniemia inducing cellular metabolic alterations, prolonged state of "neuroinflammation", activation of brain microglia, accumulation of manganese and ammonia, and systemic inflammation are the main causative factors of brain damage in liver failure. The most widely recognized neurological complications of serious hepatocellular failure include hepatic encephalopathy, diffuse cerebral edema, Wilson disease, hepatic myelopathy, acquired hepatocerebral degeneration, cirrhosis-related Parkinsonism and osmotic demyelination syndrome...
February 27, 2017: Transplantation Reviews
https://www.readbyqxmd.com/read/28282629/manganese-exposure-and-neurotoxic-effects-in-children
#10
REVIEW
Geir Bjørklund, Max Stanley Chartrand, Jan Aaseth
Manganese (Mn) is the fifth most abundant metal on earth. Although it is a well understood essential trace element, in excess, Mn is neurotoxic. Initial toxic symptoms associated with Mn are of psychiatric nature and are clinically defined as locura manganica. Neurological signs of Mn toxicity include dystonia, progressive bradykinesia, and disturbance of gait, slurring, and stuttering of speech with diminished volume. Studies indicate that children who ingested Mn in the drinking water (WMn) at or above a level of 0...
May 2017: Environmental Research
https://www.readbyqxmd.com/read/28279842/tooth-manganese-as-a-biomarker-of-exposure-and-body-burden-in-rats
#11
Christine Austin, Cardius Richardson, Donald Smith, Manish Arora
BACKGROUND: Neonates and children are particularly vulnerable to the toxic effects of excess manganese (Mn), but studies of Mn exposure during these developmental periods are hampered by a lack of validated biomarkers. Deciduous teeth may be used to assess Mn exposure during these developmental periods but require further validation to determine the relationship between tooth Mn, Mn in target tissues, and exposure. OBJECTIVES: To determine the relationship of tooth Mn concentrations with: (i) exposure dose, (ii) the timing/duration of exposure, and (iii) with Mn concentrations in blood, brain and bone...
May 2017: Environmental Research
https://www.readbyqxmd.com/read/28246661/whole-brain-metallomic-analysis-of-the-common-marmoset-callithrix-jacchus
#12
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
https://www.readbyqxmd.com/read/28236167/cocaine-differentially-affects-synaptic-activity-in-memory-and-midbrain-areas-of-female-and-male-rats-an-in-vivo-memri-study
#13
Pablo D Perez, Gabrielle Hall, Jasenka Zubcevic, Marcelo Febo
Manganese enhanced magnetic resonance imaging (MEMRI) has been previously used to determine the effect of acute cocaine on calcium-dependent synaptic activity in male rats. However, there have been no MEMRI studies examining sex differences in the functional neural circuits affected by repeated cocaine. In the present study, we used MEMRI to investigate the effects of repeated cocaine on brain activation in female and male rats. Adult female and male rats were scanned at 4.7 Tesla three days after final treatment with saline, a single cocaine injection (15 mg kg(-1), i...
February 24, 2017: Brain Imaging and Behavior
https://www.readbyqxmd.com/read/28230106/longitudinal-assessments-of-normal-and-perilesional-tissues-in-focal-brain-ischemia-and-partial-optic-nerve-injury-with-manganese-enhanced-mri
#14
Kevin C Chan, Iris Y Zhou, Stanley S Liu, Yolandi van der Merwe, Shu-Juan Fan, Victor K Hung, Sookja K Chung, Wu-Tian Wu, Kwok-Fai So, Ed X Wu
Although manganese (Mn) can enhance brain tissues for improving magnetic resonance imaging (MRI) assessments, the underlying neural mechanisms of Mn detection remain unclear. In this study, we used Mn-enhanced MRI to test the hypothesis that different Mn entry routes and spatiotemporal Mn distributions can reflect different mechanisms of neural circuitry and neurodegeneration in normal and injured brains. Upon systemic administration, exogenous Mn exhibited varying transport rates and continuous redistribution across healthy rodent brain nuclei over a 2-week timeframe, whereas in rodents following photothrombotic cortical injury, transient middle cerebral artery occlusion, or neonatal hypoxic-ischemic brain injury, Mn preferentially accumulated in perilesional tissues expressing gliosis or oxidative stress within days...
February 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28222320/antioxidant-polymorphisms-do-not-influence-the-risk-of-epilepsy-or-its-drug-resistance-after-neonatal-hypoxic-ischemic-brain-injury
#15
Katarina Esih, Katja Goričar, Vita Dolžan, Zvonka Rener-Primec
PURPOSE: The aim of this study was to investigate if common functional antioxidant polymorphisms are associated with epilepsy after neonatal hypoxic-ischemic encephalopathy (HIE). The antioxidant enzymes manganese superoxide dismutase (SOD2), glutathione peroxidase 1 (GPX1) and catalase (CAT) represent the primary defence mechanism against reactive oxygen species (ROS). Evidence suggests that genetic variants in antioxidant enzymes could influence susceptibility to epilepsy, but to date the relationship between them remains unclear...
March 2017: Seizure: the Journal of the British Epilepsy Association
https://www.readbyqxmd.com/read/28220999/drosophila-divalent-metal-ion-transporter-malvolio-is-required-in-dopaminergic-neurons-for-feeding-decisions
#16
E Søvik, A LaMora, G Seehra, A B Barron, J G Duncan, Y Ben-Shahar
Members of the natural resistance-associated macrophage protein (NRAMP) family are evolutionarily conserved metal ion transporters that play an essential role in regulating intracellular divalent cation homeostasis in both prokaryotes and eukaryotes. Malvolio (Mvl), the sole NRAMP family member in insects, plays a role in food choice behaviors in Drosophila and other species. However, the specific physiological and cellular processes that require the action of Mvl for appropriate feeding decisions remain elusive...
February 21, 2017: Genes, Brain, and Behavior
https://www.readbyqxmd.com/read/28213125/reduced-bioavailable-manganese-causes-striatal-urea-cycle-pathology-in-huntington-s-disease-mouse-model
#17
Terry Jo V Bichell, Michal Wegrzynowicz, K Grace Tipps, Emma M Bradley, Michael A Uhouse, Miles Bryan, Kyle Horning, Nicole Fisher, Karrie Dudek, Timothy Halbesma, Preethi Umashanker, Andrew D Stubbs, Hunter K Holt, Gunnar F Kwakye, Andrew M Tidball, Roger J Colbran, Michael Aschner, M Diana Neely, Alba Di Pardo, Vittorio Maglione, Alexander Osmand, Aaron B Bowman
Huntington's disease (HD) is caused by a mutation in the huntingtin gene (HTT), resulting in profound striatal neurodegeneration through an unknown mechanism. Perturbations in the urea cycle have been reported in HD models and in HD patient blood and brain. In neurons, arginase is a central urea cycle enzyme, and the metal manganese (Mn) is an essential cofactor. Deficient biological responses to Mn, and reduced Mn accumulation have been observed in HD striatal mouse and cell models. Here we report in vivo and ex vivo evidence of a urea cycle metabolic phenotype in a prodromal HD mouse model...
February 14, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28212723/redox-dynamics-of-manganese-as-a-mitochondrial-life-death-switch
#18
REVIEW
Matthew Ryan Smith, Jolyn Fernandes, Young-Mi Go, Dean P Jones
Sten Orrenius, M.D., Ph.D., pioneered many areas of cellular and molecular toxicology and made seminal contributions to our knowledge of oxidative stress and glutathione (GSH) metabolism, organellar functions and Ca(+2)-dependent mechanisms of cell death, and mechanisms of apoptosis. On the occasion of his 80(th) birthday, we summarize current knowledge on redox biology of manganese (Mn) and its role in mechanisms of cell death. Mn is found in all organisms and has critical roles in cell survival and death mechanisms by regulating Mn-containing enzymes such as manganese superoxide dismutase (SOD2) or affecting expression and activity of caspases...
January 15, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28205254/manganese-and-selenium-concentrations-in-cerebrospinal-fluid-of-seriously-ill-children
#19
Tomáš Franěk, Karel Kotaška, Richard Průša
BACKGROUND: The homeostasis of essential trace elements such as selenium and manganese may be altered in patients with severe diseases of various etiologies (trauma brain injuries, tumors, leukemias, lymphomas, neurological diseases). METHODS: Concentration of manganese and selenium were determined in cerebrospinal fluid by electrothermal atomic absorption spectrometry in 50 hospitalized children with various clinical ethiologies including oncological, neurological, and brain related diseases...
February 15, 2017: Journal of Clinical Laboratory Analysis
https://www.readbyqxmd.com/read/28193543/reduction-of-manganese-intake-improves-neuropsychological-manifestations-in-rats-with-minimal-hepatic-encephalopathy
#20
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
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