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https://www.readbyqxmd.com/read/29688240/nanoscale-synchrotron-x-ray-speciation-of-iron-and-calcium-compounds-in-amyloid-plaque-cores-from-alzheimer-s-disease-subjects
#1
James Everett, Joanna F Collingwood, Vindy Tjendana-Tjhin, Jake Brooks, Frederik Lermyte, Germán Plascencia-Villa, Ian Hands-Portman, Jon Dobson, George Perry, Neil D Telling
Altered metabolism of biometals in the brain is a key feature of Alzheimer's disease, and biometal interactions with amyloid-β are linked to amyloid plaque formation. Iron-rich aggregates, including evidence for the mixed-valence iron oxide magnetite, are associated with amyloid plaques. To test the hypothesis that increased chemical reduction of iron, as observed in vitro in the presence of aggregating amyloid-β, may occur at sites of amyloid plaque formation in the human brain, the nanoscale distribution and physicochemical states of biometals, particularly iron, were characterised in isolated amyloid plaque cores from human Alzheimer's disease cases using synchrotron X-ray spectromicroscopy...
April 24, 2018: Nanoscale
https://www.readbyqxmd.com/read/29681846/high-dietary-iron-supplement-induces-the-nigrostriatal-dopaminergic-neurons-lesion-in-transgenic-mice-expressing-mutant-a53t-human-alpha-synuclein
#2
Fengju Jia, Ning Song, Weiwei Wang, Xixun Du, Yajing Chi, Hong Jiang
Both alpha-synuclein aggregation and iron deposits are neuropathological hallmarks of Parkinson's disease (PD). We are particularly interested in whether iron could synergize with alpha-synuclein pathology in vivo , especially in the nigrostriatal system. In the present study, we reported transgenic mice with overexpressing human A53T alpha-synuclein, as well as WT mice with high dietary iron displayed hyperactive motor coordination and impaired colonic motility, compared with those with basal dietary iron...
2018: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/29681108/functional-mrna-analysis-reveals-aberrant-splicing-caused-by-novel-intronic-mutation-in-wdr45-in-nbia-patient
#3
Josh Willoughby, Celia Duff-Farrier, Archana Desurkar, Manju Kurian, Ashok Raghavan, Meena Balasubramanian
WDR45 gene-associated neurodegeneration with brain iron accumulation (NBIA), referred to as beta-propeller protein-associated neurodegeneration (BPAN), is a rare disorder that presents with a very nonspecific clinical phenotype in children constituting global developmental delay. This case report illustrates the power of a combination of trio exome sequencing, in silico splicing analysis, and mRNA analysis to provide sufficient evidence for pathogenicity of a relatively intronic variant in WDR45, and in so doing, find a genetic diagnosis for a 6-year-old patient with developmental delay and seizures, a diagnosis which may otherwise have only been found once the characteristic MRI patterns of the disease became more obvious in young adulthood...
May 2018: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/29680437/treatment-of-restless-legs-syndrome-willis-ekbom-disease-with-the-non-selective-ent1-ent2-inhibitor-dipyridamole-testing-the-adenosine-hypothesis
#4
Diego Garcia-Borreguero, Xavier Guitart, Celia Garcia Malo, Irene Cano-Pumarega, Juan José Granizo, Sergi Ferré
OBJECTIVES: Recent animal models of restless legs syndrome (RLS) suggest that brain iron deficiency is associated with a hypoadenosinergic state, with downregulation of adenosine A1 receptors (A1R) in the striatum and cortex. We hypothesized that an increase in extracellular adenosine induced by inhibitors of adenosine transporters, such as the non-selective ENT1/ENT2 inhibitor dipyridamole, would result in an improvement in RLS symptoms. METHODS: In a prospective two-month open-label, non-placebo controlled clinical trial, 15 untreated idiopathic RLS patients began treatment with 100 mg dipyridamole (with uptitration to 400 mg if necessary)...
May 2018: Sleep Medicine
https://www.readbyqxmd.com/read/29680420/restless-legs-syndrome-is-associated-with-major-comorbidities-in-a-population-of-danish-blood-donors
#5
Maria Didriksen, Richard P Allen, Brendan J Burchell, Lise W Thørner, Andreas S Rigas, Emanuele Di Angelantonio, Maria H Nielsen, Poul J Jennum, Thomas Werge, Christian Erikstrup, Ole B Pedersen, Kaspar Nielsen, Mie T Bruun, Kristoffer S Burgdorf, Erik Sørensen, Henrik Ullum
BACKGROUND: Restless Legs Syndrome (RLS) is characterized by uncomfortable nocturnal sensations in the legs making sedentary activities and sleep difficult, and is thus linked with psychosocial distress. Due to the symptomatology and neurobiology of RLS (disrupting brain iron and dopamine) it is likely that RLS associates with poorer health-related quality of life (HRQL) and depressive disorder. The objective of this study was to investigate the RLS-HRQL and the RLS-depressive disorder links in a generally healthy population that is not biased by medications...
May 2018: Sleep Medicine
https://www.readbyqxmd.com/read/29679161/present-and-future-of-ultra-high-field-mri-in-neurodegenerative-disorders
#6
REVIEW
Graziella Donatelli, Roberto Ceravolo, Daniela Frosini, Michela Tosetti, Ubaldo Bonuccelli, Mirco Cosottini
PURPOSE OF REVIEW: With a high signal-to-noise ratio, unparalleled spatial resolution, and improved contrasts, ultra-high field MR (≥ 7 T) has great potential in depicting the normal radiological anatomy of smaller structures in the brain and can also provide more information about morphological, quantitative, and metabolic changes associated with a wide range of brain disorders. By focusing attention on specific brain regions believed to be associated with early pathological change, or by more closely inspecting recognized foci of brain pathology, ultra-high field MR can improve the accuracy and sensitivity of neuroimaging...
April 20, 2018: Current Neurology and Neuroscience Reports
https://www.readbyqxmd.com/read/29678591/ferroptosis-is-newly-characterized-form-of-neuronal-cell-death-in-response-to-arsenite-exposure
#7
Qianghu Tang, LuLu Bai, Zhen Zou, Pan Meng, Yinyin Xia, Shuqun Cheng, Shaoyu Mu, Jianrong Zhou, Xuefeng Wang, Xia Qin, Xianqing Cao, Xuejun Jiang, Chengzhi Chen
Ferroptosis is a novel iron-dependent form of cell death implicated in brain pathology. However, whether arsenite is an inducer of ferroptosis in the neurons remains completely unknown. In this study, the seven-week-old healthy C57BL/6 J male mice were treated with environmental related doses (0.5, 5 and 50 mg/L) of arsenite for 6 months via drinking water, and the ferroptosis-related indicators were further determined. Our results demonstrated for the first time that, arsenite exposure significantly reduced the number of neuron and caused the pathological changes of mitochondria in the cerebral cortex of mice...
April 17, 2018: Neurotoxicology
https://www.readbyqxmd.com/read/29672865/dietary-iron-fortification-normalizes-fetal-hematology-hepcidin-and-iron-distribution-in-a-rat-model-of-prenatal-alcohol-exposure
#8
Shane M Huebner, Kaylee K Helfrich, Nipun Saini, Sharon E Blohowiak, Adrienne A Cheng, Pamela J Kling, Susan M Smith
BACKGROUND: Prenatal alcohol exposure (PAE) causes neurodevelopmental disability. Clinical and animal studies show gestational iron deficiency exacerbates PAE's behavioral and growth deficits. In rat, PAE manifests an inability to establish iron homeostasis, increasing hepcidin (maternal and fetal) and fetal liver iron while decreasing brain iron and promoting anemia. Here, we hypothesize dietary iron fortification during pregnancy may mitigate alcohol's disruption of fetal iron homeostasis...
April 19, 2018: Alcoholism, Clinical and Experimental Research
https://www.readbyqxmd.com/read/29665379/superparamagnetic-iron-oxide-loaded-lipid-nanocarriers-incorporated-in-thermosensitive-in-situ-gel-for-magnetic-brain-targeting-of-clonazepam
#9
Haidy Abbas, Hanan Refai, Nesrine El Sayed
The objective of the study was to target clonazepam (CZ) to the brain through the intranasal olfactory mucosa using nanolipid carriers loaded with superparamagnetic iron oxide nanoparticles (SPION) to allow nanocarrier guidance and retention with an external magnetic field. For improved delivery the nanolipid carriers were incorporated in a thermosensitive mucoadhesive in situ gel. Different nanolipid carriers including solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) were prepared and characterized with respect to particle size, zeta potential, entrapment efficiency and in vitro release...
April 14, 2018: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/29663939/brain-iron-distribution-after-multiple-doses-of-ultra-small-superparamagnetic-iron-oxide-particles-in-rats
#10
Andrew W Gorman, Kofi M Deh, Caspar M Schwiedrzik, Julie R White, Ernest Victor Groman, Clark A Fisher, Kelly M Gillen, Pascal Spincemaille, Skye Rasmussen, Martin R Prince, Henning U Voss, Winrich A Freiwald, Yi Wang
The purpose of this study is to determine the effects of high cumulative doses of ultra-small paramagnetic iron oxide (USPIO) used in neuroimaging studies. We intravenously administered 8 mg/kg of 2 USPIO compounds daily for 4 wk to male Sprague-Dawley rats (Crl:SD). Multiecho gradient-echo MRI, serum iron levels, and histology were performed at the end of dosing and after a 7-d washout period. R2* maps and quantitative susceptibility maps (QSM) were generated from multiecho gradient-echo data. R2* maps and QSM showed iron accumulation in brain ventricles on MR images acquired at the 4- and 5-wk time points...
April 2, 2018: Comparative Medicine
https://www.readbyqxmd.com/read/29659961/multi-copper-ferroxidase-deficient-mice-have-increased-brain-iron-concentrations-and-learning-and-memory-deficits
#11
Jiashuo Zheng, Ruiwei Jiang, Min Chen, Zaitunamu Maimaitiming, Junzhuo Wang, Gregory J Anderson, Chris D Vulpe, Joshua L Dunaief, Huijun Chen
Background: The accumulation of iron occurs in the central nervous system (CNS) in several neurodegenerative diseases. Although multi-copper ferroxidases (MCFs) play an important role in cellular iron metabolism and homeostasis, the mechanism of MCFs in the CNS remains unclear. Objective: The aim was to study the role of MCFs in CNS iron metabolism and homeostasis by using hephaestin/ceruloplasmin (Heph/Cp) double knockout (KO) mice. Methods: Heph/Cp double KO male mice were generated by crossing both single KO mice...
April 1, 2018: Journal of Nutrition
https://www.readbyqxmd.com/read/29644335/neuromelanin-detection-by-magnetic-resonance-imaging-mri-and-its-promise-as-a-biomarker-for-parkinson-s-disease
#12
REVIEW
David Sulzer, Clifford Cassidy, Guillermo Horga, Un Jung Kang, Stanley Fahn, Luigi Casella, Gianni Pezzoli, Jason Langley, Xiaoping P Hu, Fabio A Zucca, Ioannis U Isaias, Luigi Zecca
The diagnosis of Parkinson's disease (PD) occurs after pathogenesis is advanced and many substantia nigra (SN) dopamine neurons have already died. Now that therapies to block this neuronal loss are under development, it is imperative that the disease be diagnosed at earlier stages and that the response to therapies is monitored. Recent studies suggest this can be accomplished by magnetic resonance imaging (MRI) detection of neuromelanin (NM), the characteristic pigment of SN dopaminergic, and locus coeruleus (LC) noradrenergic neurons...
2018: NPJ Parkinson's Disease
https://www.readbyqxmd.com/read/29643211/microbial-decay-analysis-challenges-interpretation-of-putative-organ-systems-in-cambrian-fuxianhuiids
#13
Jianni Liu, Michael Steiner, Jason A Dunlop, Degan Shu
The Chengjiang fossil Lagerstätte (Cambrian Stage 3) from Yunnan, southern China is renowned for its soft-tissue preservation. Accordingly structures in fuxianhuiids, radiodontans and great appendage arthropods have been interpreted as the nervous and cardiovascular systems, including brains, hearts and blood vessels. That such delicate organ systems survive the fossilization process seems remarkable; given that this mode of preservation involves major taphonomic changes, such as flattening, microbial degradation, chemical alteration and replacement...
April 11, 2018: Proceedings. Biological Sciences
https://www.readbyqxmd.com/read/29643036/-quantitative-magnetic-resonance-imaging-of-brain-iron-deposition-comparison-between-quantitative-susceptibility-mapping-and-transverse-relaxation-rate-r2-mapping
#14
Ji-Jing Guan, Yan-Qiu Feng
OBJECTIVE: To evaluate the accuracy and sensitivity of quantitative susceptibility mapping (QSM) and transverse relaxation rate (R2*) mapping in the measurement of brain iron deposition. METHODS: Super paramagnetic iron oxide (SPIO) phantoms and mouse models of Parkinson's disease (PD) related to iron deposition in the substantia nigra (SN) underwent 7.0 T magnetic resonance (MR) scans (Bruker, 70/16) with a multi-echo 3D gradient echo sequence, and the acquired data were processed to obtain QSM and R2*...
March 20, 2018: Nan Fang Yi Ke da Xue Xue Bao, Journal of Southern Medical University
https://www.readbyqxmd.com/read/29625173/brain-mitochondrial-iron-accumulates-in-huntington-s-disease-mediates-mitochondrial-dysfunction-and-can-be-removed-pharmacologically
#15
Sonal Agrawal, Julia Fox, Baskaran Thyagarajan, Jonathan Fox
Mitochondrial bioenergetic dysfunction is involved in neurodegeneration in Huntington's disease (HD). Iron is critical for normal mitochondrial bioenergetics but can also contribute to pathogenic oxidation. The accumulation of iron in the brain occurs in mouse models and in human HD. Yet the role of mitochondria-related iron dysregulation as a contributor to bioenergetic pathophysiology in HD is unclear. We demonstrate here that human HD and mouse model HD (12-week R6/2 and 12-month YAC128) brains accumulated mitochondrial iron and showed increased expression of iron uptake protein mitoferrin 2 and decreased iron-sulfur cluster synthesis protein frataxin...
April 3, 2018: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/29624734/predominant-role-of-microglia-in-brain-iron-retention-in-sanfilippo-syndrome-a-pediatric-neurodegenerative-disease
#16
Vincent Puy, Walaa Darwiche, Stéphanie Trudel, Cathy Gomila, Christelle Lony, Laurent Puy, Thibaud Lefebvre, Sandrine Vitry, Agnès Boullier, Zoubida Karim, Jérôme Ausseil
Neuroinflammation and iron accumulation are hallmarks of a variety of adult neurodegenerative diseases. In Sanfilippo syndrome (mucopolysaccharidosis type III, MPSIII, a pediatric neurodegenerative disease that shares some features with adult neurodegenerative diseases), the progressive accumulation of heparan sulfate oligosaccharides (HSOs) induces microglia and astrocytes to produce pro-inflammatory cytokines leading to severe neuroinflammation. The objectives of the present study were (1) to measure the local iron concentration and to assess iron metabolism in the brain of a MPSIIIB murine model and (2) to identify the brain cells involved in this accumulation...
April 6, 2018: Glia
https://www.readbyqxmd.com/read/29623644/intranasal-instillation-of-iron-oxide-nanoparticles-induces-inflammation-and-perturbation-of-trace-elements-and-neurotransmitters-but-not-behavioral-impairment-in-rats
#17
Dalel Askri, Souhir Ouni, Said Galai, Josiane Arnaud, Benoit Chovelon, Sylvia G Lehmann, Nathalie Sturm, Mohsen Sakly, Michel Sève, Salem Amara
Over the last decades, engineered nanomaterials have been widely used in various applications due to their interesting properties. Among them, iron oxide nanoparticles (IONPs) are used as theranostic agents for cancer, and also as contrast agents in magnetic resonance imaging. With the increasing production and use of these IONPs, there is an evident raise of IONP exposure and subsequently a higher risk of adverse outcome for humans and the environment. In this work, we aimed to investigate the effects of sub-acute IONP exposure on Wistar rat, particularly (i) on the emotional and learning/memory behavior, (ii) on the hematological and biochemical parameters, (iii) on the neurotransmitter content, and (vi) on the trace element homeostasis...
April 5, 2018: Environmental Science and Pollution Research International
https://www.readbyqxmd.com/read/29620288/differentiation-of-genetically-modified-canine-bone-mesenchymal-stem-cells-labeled-with-superparamagnetic-iron-oxide-into-neural%C3%A2-like-cells
#18
Xing-Long Liu, Qing-Quan Zu, Bin Wang, Shan-Shan Lu, Xiao-Quan Xu, Sheng Liu, Hai-Bin Shi
The use of mesenchymal stem cells (MSCs) has been reported to improve outcomes in various types of nervous system diseases, primarily based on their neural regenerative differentiation ability and paracrine effect on different neuroprotective cytokines. Genetically modified MSCs may enhance the paracrine effect and may further improve the cell‑based therapeutic outcome of nervous system diseases. Magnetic resonance imaging has been used to monitor distribution and migration of cells labeled with superparamagnetic iron oxide (SPIO) nanoparticles...
April 5, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29619158/a-pilot-trial-of-deferiprone-in-pantothenate-kinase-associated-neurodegeneration-patients
#19
Mohammad Rohani, Saeed Razmeh, Gholam Ali Shahidi, Elham Alizadeh, Maryam Orooji
Pantothenate kinase-associated neurodegeneration (PKAN) is the most common form of neurodegeneration with brain iron accumulation, it is an autosomal recessive disease due to mutation in PANK 2 on chromosome 20, which causes the accumulation of iron in basal ganglia and production of free radicals that cause degeneration of the cells. Deferiprone is an iron chelator that was used in treatment of thalassemia patients, it can cross the blood-brain barrier and reverse the iron deposition in the brain. Five patients with genetically confirmed PKAN received 15 mg/kg deferiprone twice daily...
December 11, 2017: Neurology International
https://www.readbyqxmd.com/read/29617109/targeted-brain-delivery-of-rabies-virus-glycoprotein-29-modified-deferoxamine-loaded-nanoparticles-reverses-functional-deficits-in-parkinsonian-mice
#20
Linhao You, Jing Wang, Tianqing Liu, Yinlong Zhang, Xuexiang Han, Ting Wang, Shanshan Guo, Tianyu Dong, Junchao Xu, Gregory J Anderson, Qiang Liu, Yan-Zhong Chang, Xin Lou, Guangjun Nie
Excess iron deposition in the brain often causes oxidative stress-related damage and necrosis of dopaminergic neurons in the substantia nigra and has been reported to be one of the major vulnerability factors in Parkinson's disease (PD). Iron chelation therapy using deferoxamine (DFO) may inhibit this nigrostriatal degeneration and prevent the progress of PD. However, DFO shows very short half-life in vivo and hardly penetrates the blood brain barrier (BBB). Hence, it is of great interest to develop DFO formulations for safe and efficient intracerebral drug delivery...
April 4, 2018: ACS Nano
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