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iron in the brain

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https://www.readbyqxmd.com/read/28204974/lipid-peroxidation-dependent-cell-death-regulated-by-gpx4-and-ferroptosis
#1
Hirotaka Imai, Masaki Matsuoka, Takeshi Kumagai, Taro Sakamoto, Tomoko Koumura
Glutathione peroxidase 4 (Phospholipid hydroperoxide glutathione peroxidase, PHGPx) can directly reduce phospholipid hydroperoxide. Depletion of GPx4 induces lipid peroxidation-dependent cell death in embryo, testis, brain, liver, heart, and photoreceptor cells of mice. Administration of vitamin E in tissue specific GPx4 KO mice restored tissue damage in testis, liver, and heart. These results indicate that suppression of phospholipid peroxidation is essential for cell survival in normal tissues in mice. Ferroptosis is an iron-dependent non-apoptotic cell death that can elicited by pharmacological inhibiting the cystine/glutamate antiporter, system Xc(-) (type I) or directly binding and loss of activity of GPx4 (Type II) in cancer cells with high level RAS-RAF-MEK pathway activity or p53 expression, but not in normal cells...
February 16, 2017: Current Topics in Microbiology and Immunology
https://www.readbyqxmd.com/read/28202542/m%C3%A3-ssbauer-spectra-of-mouse-hearts-reveal-age-dependent-changes-in-mitochondrial-and-ferritin-iron-levels
#2
Joshua D Wofford, Mrinmoy Chakrabarti, Paul Alan Lindahl
Cardiac function requires continuous high levels of energy, and so iron, a critical player in mitochondrial respiration, is an important component of the heart. Hearts from (57)Fe-enriched mice were evaluated by Mossbauer spectroscopy. Spectra consisted of a sextet and two quadrupole doublets. One doublet was due to residual blood while the other was due to [Fe4S4](2+) clusters and Fe(II) hemes, most of which were associated with mitochondrial respiration. The sextet was due to ferritin; there was no evidence of hemosiderin, a ferritin decomposition product...
February 15, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28199888/in%C3%A2-vivo-assessment-of-iron-content-of-the-cerebral-cortex-in-healthy-aging-using-7-tesla-t2-weighted-phase-imaging
#3
Mathijs Buijs, Nhat Trung Doan, Sanneke van Rooden, Maarten J Versluis, Baldur van Lew, Julien Milles, Jeroen van der Grond, Mark A van Buchem
Accumulation of brain iron has been suggested as a biomarker of neurodegeneration. Increased iron has been seen in the cerebral cortex in postmortem studies of neurodegenerative diseases and healthy aging. Until recently, the diminutive thickness of the cortex and its relatively low iron content have hampered in vivo study of cortical iron accumulation. Using phase images of a T2*-weighted sequence at ultrahigh field strength (7 Tesla), we examined the iron content of 22 cortical regions in 70 healthy subjects aged 22-80 years...
September 15, 2016: Neurobiology of Aging
https://www.readbyqxmd.com/read/28196427/neurocognitive-function-is-associated-with-serum-iron-status-in-early-adolescents
#4
Xiaopeng Ji, Naixue Cui, Jianghong Liu
OBJECTIVE: The association between iron and neurocognition remains underexplored in adolescents, and the neurocognitive effects of low and high iron levels have yet to be established. The aim of this study was to investigate the relationships of low and high iron levels with neurocognitive domains in early adolescents. METHOD: The sample comprised 428 adolescents (12.0 ± 0.4 years) from Jintan, China. Serum iron concentrations were analyzed from venous blood samples and classified into low, normal, and high levels according to the clinical reference range 75-175 μg/dl...
January 1, 2017: Biological Research for Nursing
https://www.readbyqxmd.com/read/28195347/characterization-of-ferroptosis-in-murine-models-of-hemochromatosis
#5
Hao Wang, Peng An, Enjun Xie, Qian Wu, Xuexian Fang, Hong Gao, Zhuzhen Zhang, Yuzhu Li, Xudong Wang, Jiaying Zhang, Guoli Li, Lei Yang, Wei Liu, Junxia Min, Fudi Wang
Ferroptosis is a recently identified iron-dependent form of non-apoptotic cell death implicated in brain, kidney, and heart pathology. However, the biological roles of iron and iron metabolism in ferroptosis remain poorly understood. Here, we studied the functional role of iron and iron metabolism in the pathogenesis of ferroptosis. We found that ferric citrate potently induces ferroptosis in murine primary hepatocytes and bone marrow-derived macrophages (BMDMs). Next, we screened for ferroptosis in mice fed a high-iron diet and in mouse models of hereditary hemochromatosis with iron overload...
February 13, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28193901/exceedingly-small-iron-oxide-nanoparticles-as-positive-mri-contrast-agents
#6
He Wei, Oliver T Bruns, Michael G Kaul, Eric C Hansen, Mariya Barch, Agata Wiśniowska, Ou Chen, Yue Chen, Nan Li, Satoshi Okada, Jose M Cordero, Markus Heine, Christian T Farrar, Daniel M Montana, Gerhard Adam, Harald Ittrich, Alan Jasanoff, Peter Nielsen, Moungi G Bawendi
Medical imaging is routine in the diagnosis and staging of a wide range of medical conditions. In particular, magnetic resonance imaging (MRI) is critical for visualizing soft tissue and organs, with over 60 million MRI procedures performed each year worldwide. About one-third of these procedures are contrast-enhanced MRI, and gadolinium-based contrast agents (GBCAs) are the mainstream MRI contrast agents used in the clinic. GBCAs have shown efficacy and are safe to use with most patients; however, some GBCAs have a small risk of adverse effects, including nephrogenic systemic fibrosis (NSF), the untreatable condition recently linked to gadolinium (Gd) exposure during MRI with contrast...
February 13, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28193224/microrna-mir-29-controls-a-compensatory-response-to-limit-neuronal-iron-accumulation-during-adult-life-and-aging
#7
Roberto Ripa, Luca Dolfi, Marco Terrigno, Luca Pandolfini, Aurora Savino, Valeria Arcucci, Marco Groth, Eva Terzibasi Tozzini, Mario Baumgart, Alessandro Cellerino
BACKGROUND: A widespread modulation of gene expression occurs in the aging brain, but little is known as to the upstream drivers of these changes. MicroRNAs emerged as fine regulators of gene expression in many biological contexts and they are modulated by age. MicroRNAs may therefore be part of the upstream drivers of the global gene expression modulation correlated with aging and aging-related phenotypes. RESULTS: Here, we show that microRNA-29 (miR-29) is induced during aging in short-lived turquoise killifish brain and genetic antagonism of its function induces a gene-expression signature typical of aging...
February 13, 2017: BMC Biology
https://www.readbyqxmd.com/read/28190893/metalloneurochemistry-and-the-pierian-spring-shallow-draughts-intoxicate-the-brain
#8
Jacob M Goldberg, Andrei Loas, Stephen J Lippard
Metal ions perform critical and diverse functions in nervous system physiology and pathology. The field of metalloneurochemistry aims to understand the mechanistic bases for these varied roles at the molecular level. Here, we review several areas of research that illustrate progress toward achieving this ambitious goal and identify key challenges for the future. We examine the use of lithium as a mood stabilizer, the roles of mobile zinc and copper in the synapse, the interplay of nitric oxide and metals in retrograde signaling, and the regulation of iron homeostasis in the brain...
October 2016: Israel Journal of Chemistry
https://www.readbyqxmd.com/read/28187176/%C3%AE-synuclein-increases-%C3%AE-amyloid-secretion-by-promoting-%C3%AE-%C3%AE-secretase-processing-of-app
#9
Hazel L Roberts, Bernard L Schneider, David R Brown
α-Synuclein misfolding and aggregation is often accompanied by β-amyloid deposition in some neurodegenerative diseases. We hypothesised that α-synuclein promotes β-amyloid production from APP. β-Amyloid levels and APP amyloidogenic processing were investigated in neuronal cell lines stably overexpressing wildtype and mutant α-synuclein. γ-Secretase activity and β-secretase expression were also measured. We show that α-synuclein expression induces β-amyloid secretion and amyloidogenic processing of APP in neuronal cell lines...
2017: PloS One
https://www.readbyqxmd.com/read/28179164/metacognitive-ability-correlates-with-hippocampal-and-prefrontal-microstructure
#10
Micah Allen, James C Glen, Daniel Müllensiefen, Dietrich Samuel Schwarzkopf, Francesca Fardo, Darya Frank, Martina F Callaghan, Geraint Rees
The ability to introspectively evaluate our experiences to form accurate metacognitive beliefs, or insight, is an essential component of decision-making. Previous research suggests individuals vary substantially in their level of insight, and that this variation is related to brain volume and function, particularly in the anterior prefrontal cortex (aPFC). However, the neurobiological mechanisms underlying these effects are unclear, as qualitative, macroscopic measures such as brain volume can be related to a variety of microstructural features...
February 4, 2017: NeuroImage
https://www.readbyqxmd.com/read/28178997/effect-of-oxidative-stress-induced-by-intracranial-iron-overload-on-central-pain-after-spinal-cord-injury
#11
Fan Xing Meng, Jing Ming Hou, Tian Sheng Sun
BACKGROUND: Central pain (CP) is a common clinical problem in patients with spinal cord injury (SCI). Recent studies found the pathogenesis of CP was related to the remodeling of the brain. We investigate the roles of iron overload and subsequent oxidative stress in the remodeling of the brain after SCI. METHODS: We established a rat model of central pain after SCI. Rats were divided randomly into four groups: SCI, sham operation, SCI plus deferoxamine (DFX) intervention, and SCI plus nitric oxide synthase (NOS) inhibitor treatment...
February 8, 2017: Journal of Orthopaedic Surgery and Research
https://www.readbyqxmd.com/read/28177301/tracking-short-term-biodistribution-and-long-term-clearance-of-spio-tracers-in-magnetic-particle-imaging
#12
Paul Keselman, Elaine Yu, Xinyi Zhou, Patrick Goodwill, Prashant Chandrasekharan, R Matthew Ferguson, Amit Khandhar, Scott Kemp, Kannan Krishnan, Bo Zheng, Steven Conolly
Magnetic Particle Imaging (MPI) is an emerging tracer-based medical imaging modality that images non-radioactive, kidney-safe superparamagnetic iron oxide (SPIO) tracers. MPI offers quantitative, high-contrast and high-SNR images, so MPI has exceptional promise for applications such as cell tracking, angiography, brain perfusion, cancer detection, traumatic brain injury and pulmonary imaging. In assessing MPI's utility for applications mentioned above, it is important to be able to assess tracer short-term biodistribution as well as long-term clearance from the body...
February 8, 2017: Physics in Medicine and Biology
https://www.readbyqxmd.com/read/28170006/age-modulates-the-injury-induced-metallomic-profile-in-the-brain
#13
Stuart D Portbury, Dominic J Hare, Charlotte J Sgambelloni, David P Bishop, David I Finkelstein, Philip A Doble, Paul A Adlard
The biological transition metals iron (Fe), copper (Cu) and zinc (Zn) are thought to contribute to the neuronal pathologies that occur following traumatic brain injury (TBI), and indeed our previously published work in young (3 month-old) mice clearly demonstrates a significant spatiotemporal modulation of metals following TBI. Of note, however, is the literature observation that there is both an apparent detrimental effect of aging on TBI outcomes and an alteration in metals and their various transporters with normal advancing age...
February 7, 2017: Metallomics: Integrated Biometal Science
https://www.readbyqxmd.com/read/28169355/enhancement-of-5-aminolevulinic-acid-based-fluorescence-detection-of-side-population-defined-glioma-stem-cells-by-iron-chelation
#14
Wenqian Wang, Kouichi Tabu, Yuichiro Hagiya, Yuta Sugiyama, Yasuhiro Kokubu, Yoshitaka Murota, Shun-Ichiro Ogura, Tetsuya Taga
Cancer stem cells (CSCs) are dominantly responsible for tumor progression and chemo/radio-resistance, resulting in tumor recurrence. 5-aminolevulinic acid (ALA) is metabolized to fluorescent protoporphyrin IX (PpIX) specifically in tumor cells, and therefore clinically used as a reagent for photodynamic diagnosis (PDD) and therapy (PDT) of cancers including gliomas. However, it remains to be clarified whether this method could be effective for CSC detection. Here, using flow cytometry-based analysis, we show that side population (SP)-defined C6 glioma CSCs (GSCs) displayed much less 5-ALA-derived PpIX fluorescence than non-GSCs...
February 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28168364/effects-of-aging-on-formula-see-text-formula-see-text-and-qsm-mri-values-in-the-subcortex
#15
M C Keuken, P-L Bazin, K Backhouse, S Beekhuizen, L Himmer, A Kandola, J J Lafeber, L Prochazkova, A Trutti, A Schäfer, R Turner, B U Forstmann
The aging brain undergoes several anatomical changes that can be measured with Magnetic Resonance Imaging (MRI). Early studies using lower field strengths have assessed changes in tissue properties mainly qualitatively, using [Formula: see text]- or [Formula: see text]- weighted images to provide image contrast. With the development of higher field strengths (7 T and above) and more advanced MRI contrasts, quantitative measures can be acquired even of small subcortical structures. This study investigates volumetric, spatial, and quantitative MRI parameter changes associated with healthy aging in a range of subcortical nuclei, including the basal ganglia, red nucleus, and the periaqueductal grey...
February 6, 2017: Brain Structure & Function
https://www.readbyqxmd.com/read/28168129/a-quandary-of-cuprum-wilson-s-disease-disguising-as-progressive-myoclonic-epilepsy
#16
Monika Sachan, Suman Kushwaha, Shah Faisal Ahmad Tarfarosh, Vineet Banga, Ashutosh Gupta
Although metals are indispensable for the production of articles in our daily usage, the deposition of these metals in human tissue is known to cause disease. However, it is not always the ingestion of abnormal amounts of lead, iron, or copper that makes our tissues morbid; our hereditary and metabolic issues are to be blamed as well. Wilson's disease is one such hereditary disease that creates chaos in tissues, usually the brain and liver, via deposition of abnormal amounts of copper in them. While Wilson's disease almost seems to bring a picture of a young patient with dystonia and other extrapyramidal symptoms in our imagination, seizures are very uncommon in this disorder...
January 1, 2017: Curēus
https://www.readbyqxmd.com/read/28164203/modulating-motility-of-intracellular-vesicles-in-cortical-neurons-with-nanomagnetic-forces-on-chip
#17
Anja Kunze, Coleman Tylor Murray, Chanya Godzich, Jonathan Lin, Keegan Owsley, Andy Tay, Dino Di Carlo
Vesicle transport is a major underlying mechanism of cell communication. Inhibiting vesicle transport in brain cells results in blockage of neuronal signals, even in intact neuronal networks. Modulating intracellular vesicle transport can have a huge impact on the development of new neurotherapeutic concepts, but only if we can specifically interfere with intracellular transport patterns. Here, we propose to modulate motion of intracellular lipid vesicles in rat cortical neurons based on exogenously bioconjugated and cell internalized superparamagnetic iron oxide nanoparticles (SPIONs) within microengineered magnetic gradients on-chip...
February 6, 2017: Lab on a Chip
https://www.readbyqxmd.com/read/28162166/-difference-in-imaging-and-metal-metabolism-between-hepatic-and-cerebral-type-wilson-disease
#18
X X Zhou, X H Li, X Y Pu, H L Qin, X B Li, J P Chu, Z Y Yang, H W Huang, X L Liang
Objective: To evaluate the difference of metal metabolism, damage to structure and functional activity in brains between hepatic and cerebral type Wilson disease (WD). Methods: Forty patients with WD, including 20 with cerebral type and 20 with hepatic type, and 20 age-matched healthy controls in the First Affiliated Hospital, Sun Yat-sen University between Jul 2013 and May 2016 were enrolled.All study subjects underwent diffusion tensor imaging (DTI), resting state functional MRI (rs-fMRI) and susceptibility weighted imaging (SWI) of the brain...
January 17, 2017: Zhonghua Yi Xue za Zhi [Chinese medical journal]
https://www.readbyqxmd.com/read/28131884/inflammation-induced-brain-endothelial-activation-leads-to-uptake-of-electrostatically-stabilized-iron-oxide-nanoparticles-via-sulfated-glycosaminoglycans
#19
Dominique Berndt, Jason M Millward, Jörg Schnorr, Matthias Taupitz, Verena Stangl, Friedemann Paul, Susanne Wagner, Jens T Wuerfel, Ingolf Sack, Antje Ludwig, Carmen Infante-Duarte
Based on our previous data on the presence of very small superparamagnetic iron oxide nanoparticles (VSOP) on brain endothelial structures during experimental autoimmune encephalomyelitis (EAE), we investigated the mechanisms of VSOP binding on inflamed brain endothelial cells in vivo and in vitro. After intravenous application, VSOP were detected in brain endothelial cells of EAE animals at peak disease and prior to clinical onset. In vitro, inflammatory stimuli increased VSOP uptake by brain endothelial bEnd...
January 25, 2017: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/28130443/na-h-exchanger-9-regulates-iron-mobilization-at-the-blood-brain-barrier-in-response-to-iron-starvation
#20
Rami Beydoun, Mohamed A Hamood, Daniela M Gomez Zubeita, Kalyan C Kondapalli
Iron is essential for brain function, with loss of iron homeostasis in the brain linked to neurological diseases ranging from rare syndromes to more common disorders, such as Parkinson's and Alzheimer's diseases. Iron entry into the brain is regulated by the blood-brain barrier (BBB). Molecular mechanisms regulating this transport are poorly understood. Using an in vitro model of the BBB, we identify NHE9, an endosomal cation/proton exchanger, as a novel regulator of this system. Human brain microvascular endothelial cells (hBMVECs) that constitute the BBB receive brain-iron status information via paracrine signals from ensheathing astrocytes...
January 27, 2017: Journal of Biological Chemistry
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