WorldWideScience

Sample records for brain iron accumulation

  1. Self-Mutilation in Neurodegeneration with Brain Iron Accumulation.

    Science.gov (United States)

    Chandra, Sadanandavalli Retnaswami; Raj, Pawan; Issac, Thomas Gregor

    2015-01-01

    Neurodegeneration with brain iron accumulation (NBIA) is the term applied to a heterogeneous group of disorders resulting in iron deposition in the basal ganglia. Well-known phenotypic features are progressive regression with extra pyramidal involvement and a variable course. A 10-year-old child born to consanguineous parents presented with progressive generalized opisthotonic dystonia, retrocollis, oromandibular dyskinesias, apraxia for swallowing, optic atrophy and severe self-mutilation of lips. MR imaging showed brain iron accumulation. Other causes of self-mutilation were excluded. Early infantile onset, ophisthotonic dystonia with oromandibular dyskinesias and characteristic MR images are suggestive of NBIA. There is only one case reported in the literature of self-mutilation in this condition.

  2. Self-mutilation in neurodegeneration with brain iron accumulation

    Directory of Open Access Journals (Sweden)

    Sadanandavalli Retnaswami Chandra

    2015-01-01

    Full Text Available Neurodegeneration with brain iron accumulation (NBIA is the term applied to a heterogeneous group of disorders resulting in iron deposition in the basal ganglia. Well-known phenotypic features are progressive regression with extra pyramidal involvement and a variable course. A 10-year-old child born to consanguineous parents presented with progressive generalized opisthotonic dystonia, retrocollis, oromandibular dyskinesias, apraxia for swallowing, optic atrophy and severe self-mutilation of lips. MR imaging showed brain iron accumulation. Other causes of self-mutilation were excluded. Early infantile onset, ophisthotonic dystonia with oromandibular dyskinesias and characteristic MR images are suggestive of NBIA. There is only one case reported in the literature of self-mutilation in this condition.

  3. Neurodegeneration with brain iron accumulation: update on pathogenic mechanisms.

    Directory of Open Access Journals (Sweden)

    Sonia eLevi

    2014-05-01

    Full Text Available Perturbation of iron distribution is observed in many neurodegenerative disorders, including Alzheimer’s and Parkinson’s disease, but the comprehension of the metal role in the development and progression of such disorders is still very limited. The combination of more powerful brain imaging techniques and faster genomic DNA sequencing procedures has allowed the description of a set of genetic disorders characterized by a constant and often early accumulation of iron in specific brain regions and the identification of the associated genes; these disorders are now collectively included in the category of Neurodegeneration with Brain Iron Accumulation (NBIA. So far 10 different genetic forms have been described but this number is likely to increase in short time. Two forms are linked to mutations in genes directly involved in iron metabolism: Neuroferritinopathy, associated to mutations in the FTL gene and Aceruloplasminaemia, where the ceruloplasmin gene product is defective. In the other forms the connection with iron metabolism is not evident at all and the genetic data let infer the involvement of other pathways: Pank2, COASY,Pla2G6, C19orf12, and FA2H genes seem to be related to lipid metabolism and to mitochondria functioning, WDR45 and ATP13A2 genes are implicated in lysosomal and autophagosome activity, while the C2orf37 gene encodes a nucleolar protein of unknown function. There is much hope in the scientific community that the study of the NBIA forms may provide important insight as to the link between brain iron metabolism and neurodegenerative mechanisms and eventually pave the way for new therapeutic avenues also for the more common neurodegenerative disorders. In this work we will review the most recent findings in the molecular mechanisms underlining the most common forms of NBIA and analyze their possible link with brain iron metabolism.

  4. Dystonia in neurodegeneration with brain iron accumulation : outcome of bilateral pallidal stimulation

    NARCIS (Netherlands)

    Timmermann, L.; Pauls, K. A. M.; Wieland, K.; Jech, R.; Kurlemann, G.; Sharma, N.; Gill, S. S.; Haenggeli, C. A.; Hayflick, S. J.; Hogarth, P.; Leenders, K. L.; Limousin, P.; Malanga, C. J.; Moro, E.; Ostrem, J. L.; Revilla, F. J.; Santens, P.; Schnitzler, A.; Tisch, S.; Valldeoriola, F.; Vesper, J.; Volkmann, J.; Woitalla, D.; Peker, S.

    Neurodegeneration with brain iron accumulation encompasses a heterogeneous group of rare neurodegenerative disorders that are characterized by iron accumulation in the brain. Severe generalized dystonia is frequently a prominent symptom and can be very disabling, causing gait impairment, difficulty

  5. Transcranial ultrasound in neurodegeneration with brain iron accumulation (NBIA).

    Science.gov (United States)

    Liman, Jan; Wellmer, Andreas; Rostasy, Kevin; Bähr, Mathias; Kermer, Pawel

    2012-03-01

    NBIA/HSS is a neurodegenerative disorder associated with iron accumulation in specific brain regions. To date, the diagnosis is obtained by typical MRI changes followed by genetic mutation analysis. This procedure is laborious and limited to a few specially equipped medical centres. Since transcranial sonography (TCS) is widely used for the early diagnosis of PD in adults displaying parenchymal metal deposits, it is likely to be a reliable diagnostic tool for the early diagnosis of NBIA. In 7 patients with proven NBIA and 13 age-matched controls without record of neurological disease TCS was performed by an experienced ultrasound examiner. Data were analysed by two blinded investigators regarding hyperechogenicity and size of the substantia nigra (SN). SN size and hyperechogenicity was significantly increased in patients with NBIA compared to controls (students t-test: p < 0.001). TCS appears to be a non-invasive and inexpensive screening technique in patients with suspected NBIA. Performed by an experienced physician, it could enable an earlier diagnosis and pre-selection of patients for the MRI scan and genetic testing, which are still the diagnostic gold standard. Copyright © 2011 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

  6. Lithium suppression of tau induces brain iron accumulation and neurodegeneration.

    Science.gov (United States)

    Lei, P; Ayton, S; Appukuttan, A T; Moon, S; Duce, J A; Volitakis, I; Cherny, R; Wood, S J; Greenough, M; Berger, G; Pantelis, C; McGorry, P; Yung, A; Finkelstein, D I; Bush, A I

    2017-03-01

    Lithium is a first-line therapy for bipolar affective disorder. However, various adverse effects, including a Parkinson-like hand tremor, often limit its use. The understanding of the neurobiological basis of these side effects is still very limited. Nigral iron elevation is also a feature of Parkinsonian degeneration that may be related to soluble tau reduction. We found that magnetic resonance imaging T2 relaxation time changes in subjects commenced on lithium therapy were consistent with iron elevation. In mice, lithium treatment lowers brain tau levels and increases nigral and cortical iron elevation that is closely associated with neurodegeneration, cognitive loss and parkinsonian features. In neuronal cultures lithium attenuates iron efflux by lowering tau protein that traffics amyloid precursor protein to facilitate iron efflux. Thus, tau- and amyloid protein precursor-knockout mice were protected against lithium-induced iron elevation and neurotoxicity. These findings challenge the appropriateness of lithium as a potential treatment for disorders where brain iron is elevated (for example, Alzheimer's disease), and may explain lithium-associated motor symptoms in susceptible patients.

  7. Role of brain iron accumulation in cognitive dysfunction: evidence from animal models and human studies.

    Science.gov (United States)

    Schröder, Nadja; Figueiredo, Luciana Silva; de Lima, Maria Noêmia Martins

    2013-01-01

    Over the last decades, studies from our laboratory and other groups using animal models have shown that iron overload, resulting in iron accumulation in the brain, produces significant cognitive deficits. Iron accumulation in the hippocampus and the basal ganglia has been related to impairments in spatial memory, aversive memory, and recognition memory in rodents. These results are corroborated by studies showing that the administration of iron chelators attenuates cognitive deficits in a variety of animal models of cognitive dysfunction, including aging and Alzheimer's disease models. Remarkably, recent human studies using magnetic resonance image techniques have also shown a consistent correlation between cognitive dysfunction and iron deposition, mostly in the hippocampus, cortical areas, and basal ganglia. These findings may have relevant implications in the light of the knowledge that iron accumulates in brain regions of patients suffering from neurodegenerative diseases. A better understanding of the functional consequences of iron dysregulation in aging and neurological diseases may help to identify novel targets for treating memory problems that afflict a growing aging population.

  8. On the complexity of clinical and molecular bases of neurodegeneration with brain iron accumulation.

    Science.gov (United States)

    Tello, C; Darling, A; Lupo, V; Pérez-Dueñas, B; Espinós, C

    2017-05-23

    Neurodegeneration with brain iron accumulation (NBIA) is a group of inherited heterogeneous neurodegenerative rare disorders. These patients present with dystonia, spasticity, parkinsonism and neuropsychiatric disturbances, along with brain magnetic resonance imaging (MRI) evidence of iron accumulation. In sum, they are devastating disorders and to date, there is no specific treatment. Ten NBIA genes are accepted: PANK2, PLA2G6, C19orf12, COASY, FA2H, ATP13A2, WDR45, FTL, CP, and DCAF17; and nonetheless, a relevant percentage of patients remain without genetic diagnosis, suggesting that other novel NBIA genes remain to be discovered. Overlapping complex clinical pictures render an accurate differential diagnosis difficult. Little is known about the pathophysiology of NBIAs. The reported NBIA genes take part in a variety of pathways: CoA synthesis, lipid and iron metabolism, autophagy, and membrane remodeling. The next-generation sequencing revolution has achieved relevant advances in genetics of Mendelian diseases and provide new genes for NBIAs, which are investigated according to 2 main strategies: genes involved in disorders with similar phenotype and genes that play a role in a pathway of interest. To achieve an effective therapy for NBIA patients, a better understanding of the biological process underlying disease is crucial, moving toward a new age of precision medicine. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  9. Brain iron accumulation affects myelin-related molecular systems implicated in a rare neurogenetic disease family with neuropsychiatric features.

    Science.gov (United States)

    Heidari, M; Johnstone, D M; Bassett, B; Graham, R M; Chua, A C G; House, M J; Collingwood, J F; Bettencourt, C; Houlden, H; Ryten, M; Olynyk, J K; Trinder, D; Milward, E A

    2016-11-01

    The 'neurodegeneration with brain iron accumulation' (NBIA) disease family entails movement or cognitive impairment, often with psychiatric features. To understand how iron loading affects the brain, we studied mice with disruption of two iron regulatory genes, hemochromatosis (Hfe) and transferrin receptor 2 (Tfr2). Inductively coupled plasma atomic emission spectroscopy demonstrated increased iron in the Hfe-/- × Tfr2mut brain (P=0.002, n ≥5/group), primarily localized by Perls' staining to myelinated structures. Western immunoblotting showed increases of the iron storage protein ferritin light polypeptide and microarray and real-time reverse transcription-PCR revealed decreased transcript levels (P0.05). Overlap (P0.05). These results implicate myelin-related systems involved in NBIA neuropathogenesis in early responses to iron loading. This may contribute to behavioral symptoms in NBIA and hemochromatosis and is relevant to patients with abnormal iron status and psychiatric disorders involving myelin abnormalities or resistant to conventional treatments.

  10. Late-Onset Neurodegeneration with Brain Iron Accumulation with Diffusion Tensor Magnetic Resonance Imaging

    Directory of Open Access Journals (Sweden)

    Syed Omar Shah

    2012-12-01

    Full Text Available Introduction: Neuroferritinopathy is an autosomal dominant neurodegenerative disorder that includes a movement disorder, cognitive decline, and characteristic findings on brain magnetic resonance imaging (MRI due to abnormal iron deposition. Here, we present a late-onset case, along with diffusion tensor imaging (DTI. Case Presentation: We report the case of a 74-year-old Caucasian female with no significant past medical history who presented for evaluation of orofacial dyskinesia, suspected to be edentulous dyskinesia given her history of ill-fitting dentures. She had also developed slowly progressive dysarthria, dysphagia, visual hallucinations as well as stereotypic movements of her hands and feet. Results: The eye-of-the-tiger sign was demonstrated on T2 MRI. Increased fractional anisotropy and T2 hypointensity were observed in the periphery of the globus pallidus, putamen, substantia nigra, and dentate nucleus. T2 hyperintensity was present in the medial dentate nucleus and central globus pallidus. Discussion: The pallidal MRI findings were more typical of pantothenate kinase-associated neurodegeneration (PKAN, but given additional dentate and putamenal involvement, lack of retinopathy, and advanced age of onset, PKAN was less likely. Although the patient’s ferritin levels were within low normal range, her clinical and imaging features led to a diagnosis of neuroferritinopathy. Conclusion: Neurodegeneration with brain iron accumulation (NBIA is a rare cause of orofacial dyskinesia. DTI MRI can confirm abnormal iron deposition. The location of abnormal iron deposits helps in differentiating NBIA subtypes. Degeneration of the dentate and globus pallidus may occur via an analogous process given their similar T2 and DTI MRI appearance.

  11. Deficiency of Calcium-Independent Phospholipase A2 Beta Induces Brain Iron Accumulation through Upregulation of Divalent Metal Transporter 1.

    Directory of Open Access Journals (Sweden)

    Goichi Beck

    Full Text Available Mutations in PLA2G6 have been proposed to be the cause of neurodegeneration with brain iron accumulation type 2. The present study aimed to clarify the mechanism underlying brain iron accumulation during the deficiency of calcium-independent phospholipase A2 beta (iPLA2β, which is encoded by the PLA2G6 gene. Perl's staining with diaminobenzidine enhancement was used to visualize brain iron accumulation. Western blotting was used to investigate the expression of molecules involved in iron homeostasis, including divalent metal transporter 1 (DMT1 and iron regulatory proteins (IRP1 and 2, in the brains of iPLA2β-knockout (KO mice as well as in PLA2G6-knockdown (KD SH-SY5Y human neuroblastoma cells. Furthermore, mitochondrial functions such as ATP production were examined. We have discovered for the first time that marked iron deposition was observed in the brains of iPLA2β-KO mice since the early clinical stages. DMT1 and IRP2 were markedly upregulated in all examined brain regions of aged iPLA2β-KO mice compared to age-matched wild-type control mice. Moreover, peroxidized lipids were increased in the brains of iPLA2β-KO mice. DMT1 and IRPs were significantly upregulated in PLA2G6-KD cells compared with cells treated with negative control siRNA. Degeneration of the mitochondrial inner membrane and decrease of ATP production were observed in PLA2G6-KD cells. These results suggest that the genetic ablation of iPLA2β increased iron uptake in the brain through the activation of IRP2 and upregulation of DMT1, which may be associated with mitochondrial dysfunction.

  12. β-Propeller protein-associated neurodegeneration: a new X-linked dominant disorder with brain iron accumulation.

    Science.gov (United States)

    Hayflick, Susan J; Kruer, Michael C; Gregory, Allison; Haack, Tobias B; Kurian, Manju A; Houlden, Henry H; Anderson, James; Boddaert, Nathalie; Sanford, Lynn; Harik, Sami I; Dandu, Vasuki H; Nardocci, Nardo; Zorzi, Giovanna; Dunaway, Todd; Tarnopolsky, Mark; Skinner, Steven; Holden, Kenton R; Frucht, Steven; Hanspal, Era; Schrander-Stumpel, Connie; Mignot, Cyril; Héron, Delphine; Saunders, Dawn E; Kaminska, Margaret; Lin, Jean-Pierre; Lascelles, Karine; Cuno, Stephan M; Meyer, Esther; Garavaglia, Barbara; Bhatia, Kailash; de Silva, Rajith; Crisp, Sarah; Lunt, Peter; Carey, Martyn; Hardy, John; Meitinger, Thomas; Prokisch, Holger; Hogarth, Penelope

    2013-06-01

    Neurodegenerative disorders with high iron in the basal ganglia encompass an expanding collection of single gene disorders collectively known as neurodegeneration with brain iron accumulation. These disorders can largely be distinguished from one another by their associated clinical and neuroimaging features. The aim of this study was to define the phenotype that is associated with mutations in WDR45, a new causative gene for neurodegeneration with brain iron accumulation located on the X chromosome. The study subjects consisted of WDR45 mutation-positive individuals identified after screening a large international cohort of patients with idiopathic neurodegeneration with brain iron accumulation. Their records were reviewed, including longitudinal clinical, laboratory and imaging data. Twenty-three mutation-positive subjects were identified (20 females). The natural history of their disease was remarkably uniform: global developmental delay in childhood and further regression in early adulthood with progressive dystonia, parkinsonism and dementia. Common early comorbidities included seizures, spasticity and disordered sleep. The symptoms of parkinsonism improved with l-DOPA; however, nearly all patients experienced early motor fluctuations that quickly progressed to disabling dyskinesias, warranting discontinuation of l-DOPA. Brain magnetic resonance imaging showed iron in the substantia nigra and globus pallidus, with a 'halo' of T1 hyperintense signal in the substantia nigra. All patients harboured de novo mutations in WDR45, encoding a beta-propeller protein postulated to play a role in autophagy. Beta-propeller protein-associated neurodegeneration, the only X-linked disorder of neurodegeneration with brain iron accumulation, is associated with de novo mutations in WDR45 and is recognizable by a unique combination of clinical, natural history and neuroimaging features.

  13. Brain iron accumulation in unexplained fetal and infant death victims with smoker mothers-The possible involvement of maternal methemoglobinemia

    Directory of Open Access Journals (Sweden)

    Corna Melissa F

    2011-07-01

    Full Text Available Abstract Background Iron is involved in important vital functions as an essential component of the oxygen-transporting heme mechanism. In this study we aimed to evaluate whether oxidative metabolites from maternal cigarette smoke could affect iron homeostasis in the brain of victims of sudden unexplained fetal and infant death, maybe through the induction of maternal hemoglobin damage, such as in case of methemoglobinemia. Methods Histochemical investigations by Prussian blue reaction were made on brain nonheme ferric iron deposits, gaining detailed data on their localization in the brainstem and cerebellum of victims of sudden death and controls. The Gless and Marsland's modification of Bielschowsky's was used to identify neuronal cell bodies and neurofilaments. Results Our approach highlighted accumulations of blue granulations, indicative of iron positive reactions, in the brainstem and cerebellum of 33% of victims of sudden death and in none of the control group. The modified Bielschowsky's method confirmed that the cells with iron accumulations were neuronal cells. Conclusions We propose that the free iron deposition in the brain of sudden fetal and infant death victims could be a catabolic product of maternal methemoglobinemia, a biomarker of oxidative stress likely due to nicotine absorption.

  14. Transgenic Mice Overexpressing the Divalent Metal Transporter 1 Exhibit Iron Accumulation and Enhanced Parkin Expression in the Brain.

    Science.gov (United States)

    Zhang, Cheng-Wu; Tai, Yee Kit; Chai, Bing-Han; Chew, Katherine C M; Ang, Eng-Tat; Tsang, Fai; Tan, Bryce W Q; Hong, Eugenia T E; Asad, Abu Bakar Ali; Chuang, Kai-Hsiang; Lim, Kah-Leong; Soong, Tuck Wah

    2017-07-10

    Exposure to divalent metals such as iron and manganese is thought to increase the risk for Parkinson's disease (PD). Under normal circumstances, cellular iron and manganese uptake is regulated by the divalent metal transporter 1 (DMT1). Accordingly, alterations in DMT1 levels may underlie the abnormal accumulation of metal ions and thereby disease pathogenesis. Here, we have generated transgenic mice overexpressing DMT1 under the direction of a mouse prion promoter and demonstrated its robust expression in several regions of the brain. When fed with iron-supplemented diet, DMT1-expressing mice exhibit rather selective accumulation of iron in the substantia nigra, which is the principal region affected in human PD cases, but otherwise appear normal. Alongside this, the expression of Parkin is also enhanced, likely as a neuroprotective response, which may explain the lack of phenotype in these mice. When DMT1 is overexpressed against a Parkin null background, the double-mutant mice similarly resisted a disease phenotype even when fed with iron- or manganese-supplemented diet. However, these mice exhibit greater vulnerability toward 6-hydroxydopamine-induced neurotoxicity. Taken together, our results suggest that iron accumulation alone is not sufficient to cause neurodegeneration and that multiple hits are required to promote PD.

  15. Brain iron accumulation in Wilson disease: a post mortem 7 Tesla MRI - histopathological study.

    Science.gov (United States)

    Dusek, P; Bahn, E; Litwin, T; Jabłonka-Salach, K; Łuciuk, A; Huelnhagen, T; Madai, V I; Dieringer, M A; Bulska, E; Knauth, M; Niendorf, T; Sobesky, J; Paul, F; Schneider, S A; Czlonkowska, A; Brück, W; Wegner, C; Wuerfel, J

    2017-10-01

    In Wilson disease (WD), T2/T2*-weighted (T2*w) MRI frequently shows hypointensity in the basal ganglia that is suggestive of paramagnetic deposits. It is currently unknown whether this hypointensity is related to copper or iron deposition. We examined the neuropathological correlates of this MRI pattern, particularly in relation to iron and copper concentrations. Brain slices from nine WD and six control cases were investigated using a 7T-MRI system. High-resolution T2*w images were acquired and R2* parametric maps were reconstructed using a multigradient recalled echo sequence. R2* was measured in the globus pallidus (GP) and the putamen. Corresponding histopathological sections containing the lentiform nucleus were examined using Turnbull iron staining, and double staining combining Turnbull with immunohistochemistry for macrophages or astrocytes. Quantitative densitometry of the iron staining as well as copper and iron concentrations were measured in the GP and putamen and correlated with R2* values. T2*w hypointensity in the GP and/or putamen was apparent in WD cases and R2* values correlated with quantitative densitometry of iron staining. In WD, iron and copper concentrations were increased in the putamen compared to controls. R2* was correlated with the iron concentration in the GP and putamen, whereas no correlation was observed for the copper concentration. Patients with more pronounced pathological severity in the putamen displayed increased iron concentration, which correlated with an elevated number of iron-containing macrophages. T2/T2*w hypointensity observed in vivo in the basal ganglia of WD patients is related to iron rather than copper deposits. © 2016 British Neuropathological Society.

  16. Magnetic field-induced acceleration of the accumulation of magnetic iron oxide nanoparticles by cultured brain astrocytes.

    Science.gov (United States)

    Lamkowsky, Marie-Christin; Geppert, Mark; Schmidt, Maike M; Dringen, Ralf

    2012-02-01

    Magnetic iron oxide nanoparticles (Fe-NPs) are considered for various biomedical and neurobiological applications that involve the presence of external magnetic fields. However, little is known on the effects of a magnetic field on the uptake of such particles by brain cells. Cultured brain astrocytes accumulated dimercaptosuccinate-coated Fe-NP in a time-, temperature-, and concentration-dependent manner. This accumulation was strongly enhanced by the presence of the magnetic field generated by a permanent neodymium iron boron magnet that had been positioned below the cells. The magnetic field-induced acceleration of the accumulation of Fe-NP increased almost proportional to the strength of the magnetic field applied, increasing the cellular-specific iron content from an initial 10 nmol/mg protein within 4 h of incubation at 37°C to up to 12,000 nmol/mg protein. However, presence of a magnetic field also increased the amounts of iron that attached to the cells during incubation with Fe-NP at 4°C. These results suggest that the presence of an external magnetic field promotes in cultured astrocytes both the binding of Fe-NP to the cell membrane and the internalization of Fe-NP. Copyright © 2011 Wiley Periodicals, Inc.

  17. The presence of serum alters the properties of iron oxide nanoparticles and lowers their accumulation by cultured brain astrocytes

    Energy Technology Data Exchange (ETDEWEB)

    Geppert, Mark; Petters, Charlotte [University of Bremen, Centre for Biomolecular Interactions Bremen (Germany); Thiel, Karsten [Fraunhofer Institute for Manufacturing Technology and Advanced Materials (Germany); Dringen, Ralf, E-mail: ralf.dringen@uni-bremen.de [University of Bremen, Centre for Biomolecular Interactions Bremen (Germany)

    2013-01-15

    Iron oxide nanoparticles (IONPs) are considered for various diagnostic and therapeutic applications. Such particles are able to cross the blood-brain barrier and are taken up into brain cells. To test whether serum components affect the properties of IONPs and/or their uptake into brain cells, we have incubated dimercaptosuccinate-coated magnetic IONPs without and with fetal calf serum (FCS) and have exposed cultured brain astrocytes with IONPs in the absence or presence of FCS. Incubation with FCS caused a concentration-dependent increase in the average hydrodynamic diameter of the particles and of their zeta-potential. In the presence of 10 % FCS, the diameter of the IONPs increased from 57 {+-} 2 to 107 {+-} 6 nm and the zeta-potential of the particles from -22 {+-} 5 to -9 {+-} 1 mV. FCS affected also strongly the uptake of IONPs by cultured astrocytes. The efficient time- and temperature-dependent cellular accumulation of IONPs was lowered with increasing concentration of FCS by up to 90 %. In addition, in the absence of serum, endocytosis inhibitors did not alter the IONP accumulation by astrocytes, while chlorpromazine or wortmannin lowered significantly the accumulation of IONPs in the presence of FCS, suggesting that clathrin-mediated endocytosis and macropinocytosis are involved in astrocytic IONP uptake from serum-containing medium. These data demonstrate that the presence of FCS strongly affects the properties of IONPs as well as their accumulation by cultured brain cells.

  18. The presence of serum alters the properties of iron oxide nanoparticles and lowers their accumulation by cultured brain astrocytes

    Science.gov (United States)

    Geppert, Mark; Petters, Charlotte; Thiel, Karsten; Dringen, Ralf

    2013-01-01

    Iron oxide nanoparticles (IONPs) are considered for various diagnostic and therapeutic applications. Such particles are able to cross the blood-brain barrier and are taken up into brain cells. To test whether serum components affect the properties of IONPs and/or their uptake into brain cells, we have incubated dimercaptosuccinate-coated magnetic IONPs without and with fetal calf serum (FCS) and have exposed cultured brain astrocytes with IONPs in the absence or presence of FCS. Incubation with FCS caused a concentration-dependent increase in the average hydrodynamic diameter of the particles and of their zeta-potential. In the presence of 10 % FCS, the diameter of the IONPs increased from 57 ± 2 to 107 ± 6 nm and the zeta-potential of the particles from -22 ± 5 to -9 ± 1 mV. FCS affected also strongly the uptake of IONPs by cultured astrocytes. The efficient time- and temperature-dependent cellular accumulation of IONPs was lowered with increasing concentration of FCS by up to 90 %. In addition, in the absence of serum, endocytosis inhibitors did not alter the IONP accumulation by astrocytes, while chlorpromazine or wortmannin lowered significantly the accumulation of IONPs in the presence of FCS, suggesting that clathrin-mediated endocytosis and macropinocytosis are involved in astrocytic IONP uptake from serum-containing medium. These data demonstrate that the presence of FCS strongly affects the properties of IONPs as well as their accumulation by cultured brain cells.

  19. Sulforaphane rescues memory dysfunction and synaptic and mitochondrial alterations induced by brain iron accumulation.

    Science.gov (United States)

    Lavich, I C; de Freitas, B S; Kist, L W; Falavigna, L; Dargél, V A; Köbe, L M; Aguzzoli, C; Piffero, B; Florian, P Z; Bogo, M R; de Lima, M N M; Schröder, N

    2015-08-20

    Iron overload contributes to the development of neurodegeneration and the exacerbation of normal apoptosis rates, largely due to its participation in the Fenton reaction and production of reactive oxygen species (ROS). Mitochondria constitute the major intracellular source of ROS and the main target of attack by free radicals. They are dynamic organelles that bind (fusion) and divide (fission) in response to environmental stimuli, developmental status, and energy needs of the cells. Sulforaphane (SFN) is a natural compound that displays antioxidant and anti-inflammatory activities. This study aims to investigate the effects of SFN on memory deficits and changes in markers of mitochondrial function, DNM1L and OPA1, and the synaptic marker, synaptophysin, induced by neonatal iron treatment. Male rats received vehicle or carbonyl iron (30mg/kg) from the 12th to the 14th postnatal day. In adulthood, they were treated with saline or SFN (0.5 or 5mg/kg) for 14days every other day. Memory deficits were assessed using the object recognition task. DNM1L, OPA1, and synaptophysin levels in the hippocampus were quantified by Western blotting. Results showed that SFN was able to reverse iron-induced decreases in mitochondrial fission protein, DNM1L, as well as synaptophysin levels in the hippocampus, leading to a recovery of recognition memory impairment induced by iron. These findings suggest that SFN may be further investigated as potential agent for the treatment of cognitive deficits associated with neurodegenerative disorders. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

  20. Iron accumulates in Huntington's disease neurons: protection by deferoxamine.

    Directory of Open Access Journals (Sweden)

    Jianfang Chen

    Full Text Available Huntington's disease (HD is a progressive neurodegenerative disorder caused by a polyglutamine-encoding CAG expansion in the huntingtin gene. Iron accumulates in the brains of HD patients and mouse disease models. However, the cellular and subcellular sites of iron accumulation, as well as significance to disease progression are not well understood. We used independent approaches to investigate the location of brain iron accumulation. In R6/2 HD mouse brain, synchotron x-ray fluorescence analysis revealed iron accumulation as discrete puncta in the perinuclear cytoplasm of striatal neurons. Further, perfusion Turnbull's staining for ferrous iron (II combined with transmission electron microscope ultra-structural analysis revealed increased staining in membrane bound peri-nuclear vesicles in R6/2 HD striatal neurons. Analysis of iron homeostatic proteins in R6/2 HD mice revealed decreased levels of the iron response proteins (IRPs 1 and 2 and accordingly decreased expression of iron uptake transferrin receptor (TfR and increased levels of neuronal iron export protein ferroportin (FPN. Finally, we show that intra-ventricular delivery of the iron chelator deferoxamine results in an improvement of the motor phenotype in R6/2 HD mice. Our data supports accumulation of redox-active ferrous iron in the endocytic / lysosomal compartment in mouse HD neurons. Expression changes of IRPs, TfR and FPN are consistent with a compensatory response to an increased intra-neuronal labile iron pool leading to increased susceptibility to iron-associated oxidative stress. These findings, together with protection by deferoxamine, support a potentiating role of neuronal iron accumulation in HD.

  1. Mutations in DDHD1, encoding a phospholipase A1, is a novel cause of retinopathy and neurodegeneration with brain iron accumulation.

    Science.gov (United States)

    Dard, Rodolphe; Meyniel, Claire; Touitou, Valérie; Stevanin, Giovanni; Lamari, Foudil; Durr, Alexandra; Ewenczyk, Claire; Mochel, Fanny

    2017-12-01

    Defects of phospholipids remodelling and synthesis are inborn errors of metabolism responsible for various clinical presentations including spastic paraplegia, retinopathy, optic atrophy, myo- and cardiomyopathies, and osteo-cutaneous manifestations. DDHD1 encodes a phospholipase A1, which is involved in the remodelling of phospholipids. We previously described a relatively pure hereditary spastic paraplegia (HSP) phenotype associated with mutations in DDHD1. Here we report a complex form of HSP associated with retinal dystrophy and a pattern of neurodegeneration with brain iron accumulation (NBIA) on brain MRI, due to a novel homozygous mutation in DDHD1. This observation enlarges the clinical spectrum of DDHD1-associated disorders and sheds light on a new aetiology for syndromes associating retinopathy and NBIA. It also emphasizes the role of complex lipids in the retina. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  2. Iron in the brain

    Energy Technology Data Exchange (ETDEWEB)

    Galazka-Friedman, Jolanta, E-mail: jgfrie@if.pw.edu.pl [Warsaw University of Technology, Faculty of Physics (Poland); Friedman, Andrzej [Medical University of Warsaw, Department of Neurology (Poland); Bauminger, Erika R. [Hebrew University, Racah Institute of Physics (Israel)

    2009-02-15

    The results of our studies of iron in three brain structures, substantia nigra (SN), globus pallidus (GP), and hippocampus (Hip), are presented. Moessbauer spectroscopy, electron microscopy and ELISA (enzyme-linked immuno-absorbent assay) were applied. Moessbauer studies show that most of the iron in the brain is ferritin-like. The concentration of iron is similar in SN and GP, but less than half of this in Hip. ELISA studies showed that the H/L ratio of ferritin in SN and GP is also similar, but is about three times higher in Hip. These results suggest that the role of iron in SN and GP may be different from that in Hip. Electron microscopy shows that the diameters of the ferritin iron cores in the brain are smaller that in the liver (3.5 {+-} 0.5 nm vs. 6.0 {+-} 0.5 nm). Moessbauer studies yield the ratio between the concentration of iron in control and parkinsonian SN as 1.00 {+-} 0.13.

  3. Brain Iron Metabolism Dysfunction in Parkinson's Disease.

    Science.gov (United States)

    Jiang, Hong; Wang, Jun; Rogers, Jack; Xie, Junxia

    2017-05-01

    Dysfunction of iron metabolism, which includes its uptake, storage, and release, plays a key role in neurodegenerative disorders, including Parkinson's disease (PD), Alzheimer's disease, and Huntington's disease. Understanding how iron accumulates in the substantia nigra (SN) and why it specifically targets dopaminergic (DAergic) neurons is particularly warranted for PD, as this knowledge may provide new therapeutic avenues for a more targeted neurotherapeutic strategy for this disease. In this review, we begin with a brief introduction describing brain iron metabolism and its regulation. We then provide a detailed description of how iron accumulates specifically in the SN and why DAergic neurons are especially vulnerable to iron in PD. Furthermore, we focus on the possible mechanisms involved in iron-induced cell death of DAergic neurons in the SN. Finally, we present evidence in support that iron chelation represents a plausable therapeutic strategy for PD.

  4. Uptake and metabolism of iron and iron oxide nanoparticles in brain astrocytes.

    Science.gov (United States)

    Hohnholt, Michaela C; Dringen, Ralf

    2013-12-01

    Astrocytes are considered key regulators of the iron metabolism of the brain. These cells are able to rapidly accumulate iron ions and various iron-containing compounds, store iron efficiently in ferritin and also export iron. The present short review summarizes our current knowledge of the molecular mechanisms involved in the handling of iron by astrocytes. Cultured astrocytes efficiently take up iron as ferrous or ferric iron ions or as haem by specific iron transport proteins in their cell membrane. In addition, astrocytes accumulate large amounts of iron oxide nanoparticles by endocytotic mechanisms. Despite the rapid accumulation of high amounts of iron from various iron-containing sources, the viability of astrocytes is hardly affected. A rather slow liberation of iron from accumulated haem or iron oxide nanoparticles as well as the strong up-regulation of the synthesis of the iron storage protein ferritin are likely to contribute to the high resistance of astrocytes to iron toxicity. The efficient uptake of extracellular iron by cultured astrocytes as well as their strong up-regulation of ferritin after iron exposure also suggests that brain astrocytes deal well with an excess of iron and protect the brain against iron-mediated toxicity.

  5. Immunohistochemical evaluation of iron accumulation in term ...

    African Journals Online (AJOL)

    Classical immunohistochemical studies on placenta have shown that there is a linear increase in iron storage in the placenta in the first half of a normal pregnancy, however, these stocks are decreased in normal 3rd trimester placenta. Iron accumulation in term placentas of preeclamptic and normal pregnancies were ...

  6. Phosphorylation of Akt by SC79 Prevents Iron Accumulation and Ameliorates Early Brain Injury in a Model of Experimental Subarachnoid Hemorrhage

    Directory of Open Access Journals (Sweden)

    Shuangying Hao

    2016-03-01

    Full Text Available Previous studies have demonstrated that activation of Akt may alleviate early brain injury (EBI following subarachnoid hemorrhage (SAH. This study is undertaken to determine whether iron metabolism is involved in the beneficial effect of Akt activation after SAH. Therefore, we used a novel molecule, SC79, to activate Akt in an experimental Sprague–Dawley rat model of SAH. Rats were randomly divided into four groups as follows: sham, SAH, SAH + vehicle, SAH + SC79. The results confirmed that SC79 effectively enhanced the defense against oxidative stress and alleviated EBI in the temporal lobe after SAH. Interestingly, we found that phosphorylation of Akt by SC79 reduced cell surface transferrin receptor-mediated iron uptake and promoted ferroportin-mediated iron transport after SAH. As a result, SC79 administration diminished the iron content in the brain tissue. Moreover, the impaired Fe-S cluster biogenesis was recovered and loss of the activities of the Fe-S cluster-containing enzymes were regained, indicating that injured mitochondrial functions are restored to healthy levels. These findings suggest that disrupted iron homeostasis could contribute to EBI and Akt activation may regulate iron metabolism to relieve iron toxicity, further protecting neurons from EBI after SAH.

  7. Neurodegeneration with Brain Iron Accumulation

    Science.gov (United States)

    ... physical or occupational therapy, exercise physiology, and/or speech pathology. Many medications are available to treat the primary ... physical or occupational therapy, exercise physiology, and/or speech pathology. Many medications are available to treat the primary ...

  8. Blockage of mitochondrial calcium uniporter prevents iron accumulation in a model of experimental subarachnoid hemorrhage

    Energy Technology Data Exchange (ETDEWEB)

    Yan, Huiying [Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, 305 East Zhongshan Road, Nanjing 210002, Jiangsu Province (China); Hao, Shuangying; Sun, Xiaoyan [Jiangsu Key Laboratory for Molecular Medicine, Medical School of Nanjing University, 22 Hankou Road, Nanjing 210093, Jiangsu Province (China); Zhang, Dingding; Gao, Xin; Yu, Zhuang [Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, 305 East Zhongshan Road, Nanjing 210002, Jiangsu Province (China); Li, Kuanyu, E-mail: likuanyu@nju.edu.cn [Jiangsu Key Laboratory for Molecular Medicine, Medical School of Nanjing University, 22 Hankou Road, Nanjing 210093, Jiangsu Province (China); Hang, Chun-Hua, E-mail: hang_neurosurgery@163.com [Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, 305 East Zhongshan Road, Nanjing 210002, Jiangsu Province (China)

    2015-01-24

    Highlights: • Iron accumulation was involved in the acute phase following SAH. • Blockage of MCU could attenuate cellular iron accumulation following SAH. • Blockage of MCU could decrease ROS generation and improve cell energy supply following SAH. • Blockage of MCU could alleviate apoptosis and brain injury following SAH. - Abstract: Previous studies have shown that iron accumulation is involved in the pathogenesis of brain injury following subarachnoid hemorrhage (SAH) and chelation of iron reduced mortality and oxidative DNA damage. We previously reported that blockage of mitochondrial calcium uniporter (MCU) provided benefit in the early brain injury after experimental SAH. This study was undertaken to identify whether blockage of MCU could ameliorate iron accumulation-associated brain injury following SAH. Therefore, we used two reagents ruthenium red (RR) and spermine (Sper) to inhibit MCU. Sprague–Dawley (SD) rats were randomly divided into four groups including sham, SAH, SAH + RR, and SAH + Sper. Biochemical analysis and histological assays were performed. The results confirmed the iron accumulation in temporal lobe after SAH. Interestingly, blockage of MCU dramatically reduced the iron accumulation in this area. The mechanism was revealed that inhibition of MCU reversed the down-regulation of iron regulatory protein (IRP) 1/2 and increase of ferritin. Iron–sulfur cluster dependent-aconitase activity was partially conserved when MCU was blocked. In consistence with this and previous report, ROS levels were notably reduced and ATP supply was rescued; levels of cleaved caspase-3 dropped; and integrity of neurons in temporal lobe was protected. Taken together, our results indicated that blockage of MCU could alleviate iron accumulation and the associated injury following SAH. These findings suggest that the alteration of calcium and iron homeostasis be coupled and MCU be considered to be a therapeutic target for patients suffering from SAH.

  9. Manganese accumulation in the brain: MR imaging

    Energy Technology Data Exchange (ETDEWEB)

    Uchino, A.; Nomiyama, K.; Takase, Y.; Nakazono, T.; Nojiri, J.; Kudo, S. [Saga Medical School, Department of Radiology, Saga (Japan); Noguchi, T. [Kyushu University, Department of Clinical Radiology, Graduate School of Medicine, Fukuoka (Japan)

    2007-09-15

    Manganese (Mn) accumulation in the brain is detected as symmetrical high signal intensity in the globus pallidi on T1-weighted MR images without an abnormal signal on T2-weighted images. In this review, we present several cases of Mn accumulation in the brain due to acquired or congenital diseases of the abdomen including hepatic cirrhosis with a portosystemic shunt, congenital biliary atresia, primary biliary cirrhosis, congenital intrahepatic portosystemic shunt without liver dysfunction, Rendu-Osler-Weber syndrome with a diffuse intrahepatic portosystemic shunt, and patent ductus venosus. Other causes of Mn accumulation in the brain are Mn overload from total parenteral nutrition and welding-related Mn intoxication. (orig.)

  10. Abnormal brain iron homeostasis in human and animal prion disorders.

    Directory of Open Access Journals (Sweden)

    Ajay Singh

    2009-03-01

    Full Text Available Neurotoxicity in all prion disorders is believed to result from the accumulation of PrP-scrapie (PrP(Sc, a beta-sheet rich isoform of a normal cell-surface glycoprotein, the prion protein (PrP(C. Limited reports suggest imbalance of brain iron homeostasis as a significant associated cause of neurotoxicity in prion-infected cell and mouse models. However, systematic studies on the generality of this phenomenon and the underlying mechanism(s leading to iron dyshomeostasis in diseased brains are lacking. In this report, we demonstrate that prion disease-affected human, hamster, and mouse brains show increased total and redox-active Fe (II iron, and a paradoxical increase in major iron uptake proteins transferrin (Tf and transferrin receptor (TfR at the end stage of disease. Furthermore, examination of scrapie-inoculated hamster brains at different timepoints following infection shows increased levels of Tf with time, suggesting increasing iron deficiency with disease progression. Sporadic Creutzfeldt-Jakob disease (sCJD-affected human brains show a similar increase in total iron and a direct correlation between PrP and Tf levels, implicating PrP(Sc as the underlying cause of iron deficiency. Increased binding of Tf to the cerebellar Purkinje cell neurons of sCJD brains further indicates upregulation of TfR and a phenotype of neuronal iron deficiency in diseased brains despite increased iron levels. The likely cause of this phenotype is sequestration of iron in brain ferritin that becomes detergent-insoluble in PrP(Sc-infected cell lines and sCJD brain homogenates. These results suggest that sequestration of iron in PrP(Sc-ferritin complexes induces a state of iron bio-insufficiency in prion disease-affected brains, resulting in increased uptake and a state of iron dyshomeostasis. An additional unexpected observation is the resistance of Tf to digestion by proteinase-K, providing a reliable marker for iron levels in postmortem human brains. These

  11. Minocycline Attenuates Iron-Induced Brain Injury.

    Science.gov (United States)

    Zhao, Fan; Xi, Guohua; Liu, Wenqaun; Keep, Richard F; Hua, Ya

    2016-01-01

    Iron plays an important role in brain injury after intracerebral hemorrhage (ICH). Our previous study found minocycline reduces iron overload after ICH. The present study examined the effects of minocycline on the subacute brain injury induced by iron. Rats had an intracaudate injection of 50 μl of saline, iron, or iron + minocycline. All the animals were euthanized at day 3. Rat brains were used for immunohistochemistry (n = 5-6 per each group) and Western blotting assay (n = 4). Brain swelling, blood-brain barrier (BBB) disruption, and iron-handling proteins were measured. We found that intracerebral injection of iron resulted in brain swelling, BBB disruption, and brain iron-handling protein upregulation (p minocycline with iron significantly reduced iron-induced brain swelling (n = 5, p Minocycline significantly decreased albumin protein levels in the ipsilateral basal ganglia (p minocycline co-injected animals. In conclusion, the present study suggests that minocycline attenuates brain swelling and BBB disruption via an iron-chelation mechanism.

  12. Lenticular nucleus hyperechogenicity in Wilson's disease reflects local copper, but not iron accumulation.

    Science.gov (United States)

    Walter, Uwe; Skowrońska, Marta; Litwin, Tomasz; Szpak, Grażyna Maria; Jabłonka-Salach, Katarzyna; Skoloudík, David; Bulska, Ewa; Członkowska, Anna

    2014-10-01

    In patients with Wilson's disease (WD) transcranial brain sonography typically reveals areas of increased echogenicity (hyperechogenicity) of the lenticular nucleus (LN). Correlation with T2-hypointensity on magnetic resonance images suggested that LN hyperechogenicity in WD is caused by trace metal accumulation. Accumulation of both, copper and iron, in the brain of WD patients has been reported. The present study was designed to elucidate whether LN hyperechogenicity in WD reflects accumulation of copper or iron. Post-mortem brains of 15 WD patients and one non-WD subject were studied with ultrasonography in an investigator-blinded fashion. LN hyperechogenicity was measured planimetrically by manual tracing as well as using digitized image analysis. The putaminal copper content was determined in samples of 11 WD brains and the non-WD brains using inductively coupled plasma mass spectrometry, and iron content was assessed using flame atomic absorption spectroscopy. LN was normal on ultrasonography only in the non-WD brain, but abnormal (hyperechogenic) in all WD brains. Digitized image analysis measures of LN hyperechogenicity and, by trend, manual measures correlated with putaminal copper content (Pearson test; digitized: r = 0.77, p = 0.04; manual: r = 0.57, p = 0.051) but not with iron content (each, p > 0.18). LN hyperechogenicity measures were unrelated to age at death of patients, age at onset of WD, WD duration, age of brain specimen, serum copper or serum ceruloplasmin (each, p > 0.1). We conclude that LN hyperechogenicity in WD reflects copper, but not iron accumulation. Further studies are warranted to elucidate the use of transcranial brain sonography for monitoring therapeutic effects of chelating agents in WD patients.

  13. IRON, ZINC, AND FERRITIN ACCUMULATION IN COMMON BEANS

    DEFF Research Database (Denmark)

    Urbanski, Dorian Fabian; Sørensen, Kirsten; Jurkiewicz, Anna Malgorzata

    . A common nutritional base for poor populations is a staple such as maize, wheat, rice, potatoes, cassava, or beans, but many of these have low iron and zinc content as well as potent inhibitors of iron uptake. Nutritional supplements are often unavailable to such populations due to lacking infrastructure...... crops with increased nutritional value. In spite of the discovery of several genes involved in the regulation of iron and zinc metabolism in plants, the key regulators for seed iron accumulation have not yet been described. Little is known about the molecules that are responsible for chelating iron...... in mature seeds, but the ferritin protein was suggested to be the major iron storing protein in legumes [1]. Both iron and zinc localization, as well as speciation, can have an impact on their nutritional availability. We will present detailed information about iron, zinc, and ferritin distribution...

  14. Gender and iron genes may modify associations between brain iron and memory in healthy aging.

    Science.gov (United States)

    Bartzokis, George; Lu, Po H; Tingus, Kathleen; Peters, Douglas G; Amar, Chetan P; Tishler, Todd A; Finn, J Paul; Villablanca, Pablo; Altshuler, Lori L; Mintz, Jim; Neely, Elizabeth; Connor, James R

    2011-06-01

    Brain iron increases with age and is abnormally elevated early in the disease process in several neurodegenerative disorders that impact memory including Alzheimer's disease (AD). Higher brain iron levels are associated with male gender and presence of highly prevalent allelic variants in genes encoding for iron metabolism proteins (hemochromatosis H63D (HFE H63D) and transferrin C2 (TfC2)). In this study, we examined whether in healthy older individuals memory performance is associated with increased brain iron, and whether gender and gene variant carrier (IRON+) vs noncarrier (IRON-) status (for HFE H63D/TfC2) modify the associations. Tissue iron deposited in ferritin molecules can be measured in vivo with magnetic resonance imaging utilizing the field-dependent relaxation rate increase (FDRI) method. FDRI was assessed in hippocampus, basal ganglia, and white matter, and IRON+ vs IRON- status was determined in a cohort of 63 healthy older individuals. Three cognitive domains were assessed: verbal memory (delayed recall), working memory/attention, and processing speed. Independent of gene status, worse verbal-memory performance was associated with higher hippocampal iron in men (r=-0.50, p=0.003) but not in women. Independent of gender, worse verbal working memory performance was associated with higher basal ganglia iron in IRON- group (r=-0.49, p=0.005) but not in the IRON+ group. Between-group interactions (p=0.006) were noted for both of these associations. No significant associations with white matter or processing speed were observed. The results suggest that in specific subgroups of healthy older individuals, higher accumulations of iron in vulnerable gray matter regions may adversely impact memory functions and could represent a risk factor for accelerated cognitive decline. Combining genetic and MRI biomarkers may provide opportunities to design primary prevention clinical trials that target high-risk groups.

  15. Determinants of iron accumulation in deep grey matter of multiple sclerosis patients

    DEFF Research Database (Denmark)

    Ropele, Stefan; Kilsdonk, Iris D; Wattjes, Mike P

    2014-01-01

    controls were included in this multicentre study. R2* mapping was performed on 3T MRI systems. R2*in deep GM was corrected for age and was related to disease duration, disability, T2 lesion load and brain volume. RESULTS: Compared to controls, R2* was increased in all deep GM regions of MS patients except......BACKGROUND: Iron accumulation in deep grey matter (GM) structures is a consistent finding in multiple sclerosis (MS) patients. This study focused on the identification of independent determinants of iron accumulation using R2* mapping. SUBJECTS AND METHODS: Ninety-seven MS patients and 81 healthy...

  16. Iron accumulation with age, oxidative stress and functional decline.

    Directory of Open Access Journals (Sweden)

    Jinze Xu

    2008-08-01

    Full Text Available Identification of biological mediators in sarcopenia is pertinent to the development of targeted interventions to alleviate this condition. Iron is recognized as a potent pro-oxidant and a catalyst for the formation of reactive oxygen species in biological systems. It is well accepted that iron accumulates with senescence in several organs, but little is known about iron accumulation in muscle and how it may affect muscle function. In addition, it is unclear if interventions which reduced age-related loss of muscle quality, such as calorie restriction, impact iron accumulation. We investigated non-heme iron concentration, oxidative stress to nucleic acids in gastrocnemius muscle and key indices of sarcopenia (muscle mass and grip strength in male Fischer 344 X Brown Norway rats fed ad libitum (AL or a calorie restricted diet (60% of ad libitum food intake starting at 4 months of age at 8, 18, 29 and 37 months of age. Total non-heme iron levels in the gastrocnemius muscle of AL rats increased progressively with age. Between 29 and 37 months of age, the non-heme iron concentration increased by approximately 200% in AL-fed rats. Most importantly, the levels of oxidized RNA in gastrocnemius muscle of AL rats were significantly increased as well. The striking age-associated increase in non-heme iron and oxidized RNA levels and decrease in sarcopenia indices were all attenuated in the calorie restriction (CR rats. These findings strongly suggest that the age-related iron accumulation in muscle contributes to increased oxidative damage and sarcopenia, and that CR effectively attenuates these negative effects.

  17. Combined therapy of iron chelator and antioxidant completely restores brain dysfunction induced by iron toxicity

    National Research Council Canada - National Science Library

    Sripetchwandee, Jirapas; Pipatpiboon, Noppamas; Chattipakorn, Nipon; Chattipakorn, Siriporn

    2014-01-01

    .... We investigated the effects of iron overload induced by high iron-diet consumption on brain mitochondrial function, brain synaptic plasticity and learning and memory. Iron chelator (deferiprone) and antioxidant (n-acetyl cysteine...

  18. Characterization of accumulated precipitates during subsurface iron removal

    KAUST Repository

    Van Halem, Doris

    2011-01-01

    The principle of subsurface iron removal for drinking water supply is that aerated water is periodically injected into the aquifer through a tube well. On its way into the aquifer, the injected O2-rich water oxidizes adsorbed Fe 2+, creating a subsurface oxidation zone. When groundwater abstraction is resumed, the soluble Fe 2+ is adsorbed and water with reduced Fe concentrations is abstracted for multiple volumes of the injection water. In this article, Fe accumulation deposits in the aquifer near subsurface treatment wells were identified and characterized to assess the sustainability of subsurface iron removal regarding clogging of the aquifer and the potential co-accumulation of other groundwater constituents, such as As. Chemical extraction of soil samples, with Acid-Oxalate and HNO3, showed that Fe had accumulated at specific depths near subsurface iron removal wells after 12 years of operation. Whether it was due to preferred flow paths or geochemical mineralogy conditions; subsurface iron removal clearly favoured certain soil layers. The total Fe content increased between 11.5 and 390.8 mmol/kg ds in the affected soil layers, and the accumulated Fe was found to be 56-100% crystalline. These results suggest that precipitated amorphous Fe hydroxides have transformed to Fe hydroxides of higher crystallinity. These crystalline, compact Fe hydroxides have not noticeably clogged the investigated well and/or aquifer between 1996 and 2008. The subsurface iron removal wells even need less frequent rehabilitation, as drawdown increases more slowly than in normal production wells. Other groundwater constituents, such as Mn, As and Sr were found to co-accumulate with Fe. Acid extraction and ESEM-EDX showed that Ca occurred together with Fe and by X-ray Powder Diffraction it was identified as calcite. © 2010 Elsevier Ltd. All rights reserved.

  19. Disposition, accumulation and toxicity of iron fed as iron (II) sulfate or as sodium iron EDTA in rats

    NARCIS (Netherlands)

    Appel, M.J.; Kuper, C.F.; Woutersen, R.A.

    2001-01-01

    A study was performed to provide data on the disposition, accumulation and toxicity of sodium iron EDTA in comparison with iron (II) sulfate in rats on administration via the diet for 31 and 61 days. Clinical signs, body weights, food consumption, food conversion efficiency, hematology, clinical

  20. Neurodegeneration with brain iron accumulation (NBIA)

    Science.gov (United States)

    ... movement, and often death by early adulthood. Possible Complications Medicine used to treat symptoms can cause complications. ... Jankovic J, Mazziotta JC, Pomeroy SL, eds. Bradley's Neurology in Clinical Practice . 7th ed. Philadelphia, PA: Elsevier; ...

  1. Iron deficiency stimulates anthocyanin accumulation in grapevine apical leaves.

    Science.gov (United States)

    Caramanico, Leila; Rustioni, Laura; De Lorenzis, Gabriella

    2017-10-01

    Iron chlorosis is a diffuse disorder affecting Mediterranean vineyards. Beside the commonly described symptom of chlorophyll decrease, an apex reddening was recently observed. Secondary metabolites, such as anthocyanins, are often synthetized to cope with stresses in plants. The present work aimed to evaluate grapevine responses to iron deficiency, in terms of anthocyanin metabolism (reflectance spectrum, total anthocyanin content, HPLC profile and gene expression) in apical leaves of Cabernet sauvignon and Sangiovese grown in hydroponic conditions. Iron supply interruption produced after one month an increasing of anthocyanin content associated to a more stable profile in both cultivars. In Cabernet sauvignon, the higher red pigment accumulation was associated to a lower intensity of chlorotic symptoms, while in Sangiovese, despite the activation of the metabolism, the lower anthocyanin accumulation was associated to a stronger decrease in chlorophyll concentration. Gene expression data showed a significant increase of anthocyanin biosynthesis. The effects on the expression of structural and transcription factor genes of phenylpropanoid pathway were cultivar dependent. F3H, F3'H, F3'5'H and LDOX genes, in Cabernet sauvignon, and AOMT1 and AOMT genes, in Sangiovese, were positively affected by the treatment in response to iron deficiency. All data support the hypothesis of an anthocyanin biosynthesis stimulation rather than a decreased degradation of them due to iron chlorosis. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  2. Excessive early-life dietary exposure: a potential source of elevated brain iron and a risk factor for Parkinson?s disease

    OpenAIRE

    Hare, Dominic J.; Cardoso, B?rbara Rita; Raven, Erika P.; Kay L Double; Finkelstein, David I.; Ewa A. Szymlek-Gay; Biggs, Beverley-Ann

    2017-01-01

    Iron accumulates gradually in the ageing brain. In Parkinson?s disease, iron deposition within the substantia nigra is further increased, contributing to a heightened pro-oxidant environment in dopaminergic neurons. We hypothesise that individuals in high-income countries, where cereals and infant formulae have historically been fortified with iron, experience increased early-life iron exposure that predisposes them to age-related iron accumulation in the brain. Combined with genetic factors ...

  3. Iron transport across the blood-brain barrier; Development, neurovascular regulation and cerebral amyloid angiopathy

    Science.gov (United States)

    McCarthy, Ryan C; Kosman, Daniel J

    2014-01-01

    There are two barriers for iron entry into the brain: 1) the brain-cerebrospinal fluid (CSF) barrier and 2) the blood-brain barrier (BBB). Here, we review the literature on developmental iron accumulation by the brain, focusing on the transport of iron through the brain microvascular endothelial cells (BMVEC) of the BBB. We review the iron trafficking proteins which may be involved in the iron flux across BMVEC and discuss the plausible mechanisms of BMVEC iron uptake and efflux. We suggest a model for how BMVEC iron uptake and efflux are regulated and a mechanism by which the majority of iron is trafficked across the developing BBB under the direct guidance of neighboring astrocytes. Thus, we place brain iron uptake in the context of the neurovascular unit of the adult brain. Last, we propose that BMVEC iron is involved in the aggregation of amyloid-β peptides leading to the progression of cerebral amyloid angiopathy which often occurs prior to dementia and the onset of Alzheimer's disease. PMID:25355056

  4. Determinants of brain iron in multiple sclerosis A quantitative 3T MRI study

    NARCIS (Netherlands)

    Khalil, M.B.; Langkammer, C.; Ropele, S.; Petrovic, K.; Wallner-Blazek, M.; Loitfelder, M.; Jehna, M.; Bachmaier, G.; Schmidt, R.; Enzinger, C.; Fuchs, S.; Fazekas, F.

    2011-01-01

    Objectives: Abnormal high cerebral iron deposition may be implicated in chronic neurologic disorders, including multiple sclerosis (MS). R2* relaxometry has been recently validated in a postmortem study to indicate brain iron accumulation in a quantitative manner. We used this technique to assess

  5. Iron in deep brain nuclei in migraine? CAMERA follow-up MRI findings.

    Science.gov (United States)

    Palm-Meinders, Inge H; Koppen, Hille; Terwindt, Gisela M; Launer, Lenore J; van Buchem, Mark A; Ferrari, Michel D; Kruit, Mark C

    2017-07-01

    Introduction In the CAMERA population-based MRI study, migraineurs below the age of 50 had decreased T2-values indicative of increased iron deposition in several deep brain nuclei. Longer migraine history was associated with lower T2-values, suggesting an association between migraine attacks and iron accumulation. In the present nine-year follow-up study of the CAMERA cohort we re-measured the T2-values in deep brain nuclei to assess the evolution over time. Methods Baseline and follow-up T2-values measured in several basal ganglia of 128 participants (38 control, 90 migraine) were analyzed using quantitative T2 measurements and multivariate regression analysis. Results T2-values of most deep brain nuclei were increased - instead of an expected further decrease when only age-related iron accumulation would have played a role - compared to baseline (both among controls and migraineurs) and were not different in either group. In migraineurs, no differences were found by gender, migraine severity or subtype. Conclusion This study did not provide supportive data for migraine related increased iron accumulation in deep brain nuclei, but neither is it able to reject such hypotheses. Increased T2-values probably point at microstructural tissue changes that counteracted earlier accumulated iron effects. We hypothesize that, with aging, migraine-induced iron-related brain changes are obscured by other age-related tissue changes.

  6. Transferrin Receptor 2 Dependent Alterations of Brain Iron Metabolism Affect Anxiety Circuits in the Mouse.

    Science.gov (United States)

    Pellegrino, Rosa Maria; Boda, Enrica; Montarolo, Francesca; Boero, Martina; Mezzanotte, Mariarosa; Saglio, Giuseppe; Buffo, Annalisa; Roetto, Antonella

    2016-08-01

    The Transferrin Receptor 2 (Tfr2) modulates systemic iron metabolism through the regulation of iron regulator Hepcidin (Hepc) and Tfr2 inactivation causes systemic iron overload. Based on data demonstrating Tfr2 expression in brain, we analysed Tfr2-KO mice in order to examine the molecular, histological and behavioural consequences of Tfr2 silencing in this tissue. Tfr2 abrogation caused an accumulation of iron in specific districts in the nervous tissue that was not accompanied by a brain Hepc response. Moreover, Tfr2-KO mice presented a selective overactivation of neurons in the limbic circuit and the emergence of an anxious-like behaviour. Furthermore, microglial cells showed a particular sensitivity to iron perturbation. We conclude that Tfr2 is a key regulator of brain iron homeostasis and propose a role for Tfr2 alpha in the regulation of anxiety circuits.

  7. Dysregulation of cellular iron metabolism in Friedreich ataxia: from primary iron-sulfur cluster deficit to mitochondrial iron accumulation

    Directory of Open Access Journals (Sweden)

    Alain eMartelli

    2014-06-01

    Full Text Available Friedreich ataxia (FRDA is the most common recessive ataxia in the Caucasian population and is characterized by a mixed spinocerebellar and sensory ataxia frequently associating cardiomyopathy. The disease results from decreased expression of the FXN gene coding for the mitochondrial protein frataxin. Early histological and biochemical study of the pathophysiology in patient’s samples revealed that dysregulation of iron metabolism is a key feature of the disease, mainly characterized by mitochondrial iron accumulation and by decreased activity of iron-sulfur cluster enzymes. In the recent past years, considerable progress in understanding the function of frataxin has been provided through cellular and biochemical approaches, pointing to the primary role of frataxin in iron-sulfur cluster biogenesis. However, why and how the impact of frataxin deficiency on this essential biosynthetic pathway leads to mitochondrial iron accumulation is still poorly understood. Herein, we review data on both the primary function of frataxin and the nature of the iron metabolism dysregulation in FRDA. To date, the pathophysiological implication of the mitochondrial iron overload in FRDA remains to be clarified.

  8. Iron uptake and transport at the blood-brain barrier

    DEFF Research Database (Denmark)

    Larsen, Annette Burkhart; Thomsen, Louiza Bohn; Moos, Torben

    The mechanism by which iron is transported across the blood-brain barrier (BBB) remains controversial, and in this study we aimed to further clarify mechanisms by which iron is transported into the brain. We analyzed and compared the mRNA and protein expression of a variety of proteins involved...... in the transport of iron (transferrin receptor, divalent metal transporter I (DMT1), steap 2, steap 3, ceruloplasmin, hephaestin and ferroportin) in both primary rat brain capillary endothelial cells (BCEC) and immortalized rat brain capillary endothelial cell line (RBE4) grown in co-culture with defined polarity....... The mRNA expression of the iron-related molecules was also investigated in isolated brain capillaries from iron deficiency, iron reversible and normal rats. We also performed iron transport studies to analyze the routes by which iron is transported through the brain capillary endothelial cells: i) We...

  9. Iron and ferritin accumulate in separate cellular locations in Phaseolus seeds

    DEFF Research Database (Denmark)

    Cvitanich, Cristina; Przybylowicz, Wojciech J; Urbanski, Dorian Fabian

    2010-01-01

    Background Iron is an important micronutrient for all living organisms. Almost 25% of the world's population is affected by iron deficiency, a leading cause of anemia. In plants, iron deficiency leads to chlorosis and reduced yield. Both animals and plants may suffer from iron deficiency when...... their diet or environment lacks bioavailable iron. A sustainable way to reduce iron malnutrition in humans is to develop staple crops with increased content of bioavailable iron. Knowledge of where and how iron accumulates in seeds of crop plants will increase the understanding of plant iron metabolism...... and will assist in the production of staples with increased bioavailable iron. Results Here we reveal the distribution of iron in seeds of three Phaseolus species including thirteen genotypes of P. vulgaris, P. coccineus, and P. lunatus. We showed that high concentrations of iron accumulate in cells surrounding...

  10. Characterizing Brain Iron Deposition in Patients with Subcortical Vascular Mild Cognitive Impairment Using Quantitative Susceptibility Mapping: A Potential Biomarker

    OpenAIRE

    Sun, Yawen; Ge, Xin; Han, Xu; Cao, Wenwei; Wang, Yao; Ding, Weina; Cao, Mengqiu; Zhang, Yong; Xu, Qun; Zhou, Yan; Xu, Jianrong

    2017-01-01

    The presence and pattern of iron accumulation in subcortical vascular mild cognitive impairment (svMCI) and their effects on cognition have rarely been investigated. We aimed to examine brain iron deposition in svMCI subjects using quantitative susceptibility mapping (QSM). Moreover, we aimed to investigate the correlation between brain iron deposition and the severity of cognitive impairment as indicated by z-scores. We recruited 20 subcortical ischemic vascular disease (SIVD) patients who f...

  11. Iron accumulates in the lavage and explanted lungs of cystic fibrosis patients.

    Science.gov (United States)

    Abstract Oxidative stress participates in the pathophysiology of cystic fibrosis (CF). An underlying disruption in iron homeostasis can frequently be demonstrated in injuries and diseases associated with an oxidative stress. We tested the hypothesis that iron accumulation and ...

  12. Coexistence of Copper in the Iron-Rich Particles of Aceruloplasminemia Brain.

    Science.gov (United States)

    Yoshida, Kunihiro; Hayashi, Hisao; Wakusawa, Shinya; Shigemasa, Ryota; Koide, Ryoji; Ishikawa, Tetsuya; Tatsumi, Yasuaki; Kato, Koichi; Ohara, Shinji; Ikeda, Shu-Ichi

    2017-01-01

    The interaction between iron and copper has been discussed in association with human health and diseases for many years. Ceruloplasmin, a multi-copper oxidase, is mainly involved in iron metabolism and its genetic defect, aceruloplasminemia (ACP), shows neurological disorders and diabetes associated with excessive iron accumulation, but little is known about the state of copper in the brain. Here, we investigated localization of these metals in the brains of three patients with ACP using electron microscopes equipped with an energy-dispersive x-ray analyzer. Histochemically, iron deposition was observed mainly in the basal ganglia and dentate nucleus, and to lesser degree in the cerebral cortex of the patients, whereas copper grains were not detected. X-ray microanalysis identified two types of iron-rich particles in their brains: dense bodies, namely hemosiderins, and their aggregated inclusions. A small number of hemosiderins and most inclusions contained a significant amount of copper which was enough for distinct Cu x-ray images. These copper-containing particles were observed more frequently in the putamen and dentate nucleus than the cerebral cortex. Coexistence of iron and copper was supported by good correlations in the molecular ratios between these two metals in iron-rich particles with Cu x-ray image. Iron-dependent copper accumulation in iron-rich particles may suggest that copper recycling is enhanced to meet the increased requirement of cuproproteins in iron overload brain. In conclusion, the iron-rich particles with Cu x-ray image were found in the ACP brain.

  13. Excessive early-life dietary exposure: a potential source of elevated brain iron and a risk factor for Parkinson's disease.

    Science.gov (United States)

    Hare, Dominic J; Cardoso, Bárbara Rita; Raven, Erika P; Double, Kay L; Finkelstein, David I; Szymlek-Gay, Ewa A; Biggs, Beverley-Ann

    2017-01-01

    Iron accumulates gradually in the ageing brain. In Parkinson's disease, iron deposition within the substantia nigra is further increased, contributing to a heightened pro-oxidant environment in dopaminergic neurons. We hypothesise that individuals in high-income countries, where cereals and infant formulae have historically been fortified with iron, experience increased early-life iron exposure that predisposes them to age-related iron accumulation in the brain. Combined with genetic factors that limit iron regulatory capacity and/or dopamine metabolism, this may increase the risk of Parkinson's diseases. We propose to (a) validate a retrospective biomarker of iron exposure in children; (b) translate this biomarker to adults; (c) integrate it with in vivo brain iron in Parkinson's disease; and (d) longitudinally examine the relationships between early-life iron exposure and metabolism, brain iron deposition and Parkinson's disease risk. This approach will provide empirical evidence to support therapeutically addressing brain iron deposition in Parkinson's diseases and produce a potential biomarker of Parkinson's disease risk in preclinical individuals.

  14. Changes in brain amyloid-β accumulation after donepezil administration.

    Science.gov (United States)

    Ishibashi, Kenji; Miura, Yoshiharu; Wagatsuma, Kei; Ishiwata, Kiichi; Ishii, Kenji

    2017-11-01

    Recent studies using the mouse model of Alzheimer's disease (AD) have shown that donepezil administration reduces brain amyloid-β (Aβ) accumulation. This study investigated whether donepezil administration can reduce brainaccumulation in human patients with AD. Ten patients with AD underwent two (11)C-Pittsburgh Compound B positron emission tomography sessions approximately one year apart to measure brainaccumulation before and after donepezil treatment. Volumes-of-interest were placed on Aβ-preferred regions, and the standardized uptake value ratio (SUVR) was calculated considering the cerebellum as a reference region. Three and seven patients received 10mg and 5mg of donepezil, respectively. SUVR was significantly higher in the second than in the first session (P=0.026). This study showed that one year of donepezil administration does not reduce brainaccumulation in human patients with AD. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Mini-review: the morphology, mineralogy and microbiology of accumulated iron corrosion products.

    Science.gov (United States)

    Little, Brenda J; Gerke, Tammie L; Lee, Jason S

    2014-09-01

    Despite obvious differences in morphology, substratum chemistry and the electrolyte in which they form, accumulations of iron corrosion products have the following characteristics in common: stratification of iron oxides/hydroxides with a preponderance of α-FeOOH (goethite) and accumulation of metals. Bacteria, particularly iron-oxidizing and sulfate-reducing bacteria have been identified in some accumulations. Both biotic and abiotic mechanisms have been used to rationalize observations for particular sets of environmental data. This review is the first to compare observations and interpretations.

  16. The muscle protein dysferlin accumulates in the Alzheimer brain

    Science.gov (United States)

    Palamand, Divya; Strider, Jeff; Milone, Margherita; Pestronk, Alan

    2006-01-01

    Dysferlin is a transmembrane protein that is highly expressed in muscle. Dysferlin mutations cause limb-girdle dystrophy type 2B, Miyoshi myopathy and distal anterior compartment myopathy. Dysferlin has also been described in neural tissue. We studied dysferlin distribution in the brains of patients with Alzheimer disease (AD) and controls. Twelve brains, staged using the Clinical Dementia Rating were examined: 9 AD cases (mean age: 85.9 years and mean disease duration: 8.9 years), and 3 age-matched controls (mean age: 87.5 years). Dysferlin is a cytoplasmic protein in the pyramidal neurons of normal and AD brains. In addition, there were dysferlin-positive dystrophic neurites within Aβ plaques in the AD brain, distinct from tau-positive neurites. Western blots of total brain protein (RIPA) and sequential extraction buffers (high salt, high salt/Triton X-100, SDS and formic acid) of increasing protein extraction strength were performed to examine solubility state. In RIPA fractions, dysferlin was seen as 230–272 kDa bands in normal and AD brains. In serial extractions, there was a shift of dysferlin from soluble phase in high salt/Triton X-100 to the more insoluble SDS fraction in AD. Dysferlin is a new protein described in the AD brain that accumulates in association with neuritic plaques. In muscle, dysferlin plays a role in the repair of muscle membrane damage. The accumulation of dysferlin in the AD brain may be related to the inability of neurons to repair damage due to Aβ deposits accumulating in the AD brain. PMID:17024495

  17. Accumulation of silver nanoparticles by cultured primary brain astrocytes

    Energy Technology Data Exchange (ETDEWEB)

    Luther, Eva M; Koehler, Yvonne; Dringen, Ralf [Center for Biomolecular Interactions Bremen, University of Bremen, PO Box 330440, D-28334 Bremen (Germany); Diendorf, Joerg; Epple, Matthias, E-mail: ralf.dringen@uni-bremen.de [Inorganic Chemistry and Center for Nanointegration Duisburg-Essen, University of Duisburg-Essen, Universitaetsstrasse 5-7, D-45117 Essen (Germany)

    2011-09-16

    Silver nanoparticles (AgNP) are components of various food industry products and are frequently used for medical equipment and materials. Although such particles enter the vertebrate brain, little is known on their biocompatibility for brain cells. To study the consequences of an AgNP exposure of brain cells we have treated astrocyte-rich primary cultures with polyvinylpyrrolidone (PVP)-coated AgNP. The incubation of cultured astrocytes with micromolar concentrations of AgNP for up to 24 h resulted in a time- and concentration-dependent accumulation of silver, but did not compromise the cell viability nor lower the cellular glutathione content. In contrast, the incubation of astrocytes for 4 h with identical amounts of silver as AgNO{sub 3} already severely compromised the cell viability and completely deprived the cells of glutathione. The accumulation of AgNP by astrocytes was proportional to the concentration of AgNP applied and significantly lowered by about 30% in the presence of the endocytosis inhibitors chloroquine or amiloride. Incubation at 4 {sup 0}C reduced the accumulation of AgNP by 80% compared to the values obtained for cells that had been exposed to AgNP at 37 {sup 0}C. These data demonstrate that viable cultured brain astrocytes efficiently accumulate PVP-coated AgNP in a temperature-dependent process that most likely involves endocytotic pathways.

  18. The interplay between iron accumulation, mitochondrial dysfunction and inflammation during the execution step of neurodegenerative disorders

    Directory of Open Access Journals (Sweden)

    Pamela J. Urrutia

    2014-03-01

    Full Text Available A growing set of observations points to mitochondrial dysfunction, iron accumulation, oxidative damage and chronic inflammation as common pathognomonic signs of a number of neurodegenerative diseases that includes Alzheimer's disease, Huntington disease, amyotrophic lateral sclerosis, Friedrich’s ataxia and Parkinson’s disease. Particularly relevant for neurodegenerative processes is the relationship between mitochondria and iron. The mitochondrion upholds the synthesis of iron-sulfur clusters and heme, the most abundant iron-containing prosthetic groups in a large variety of proteins, so a fraction of incoming iron must go through this organelle before reaching its final destination. In turn, the mitochondrial respiratory chain is the source of reactive oxygen species (ROS derived from leaks in the electron transport chain. The co-existence of both iron and ROS in the secluded space of the mitochondrion makes this organelle particularly prone to hydroxyl radical-mediated damage. In addition, a connection between the loss of iron homeostasis and inflammation is starting to emerge; thus, inflammatory cytokines like TNF-alpha and IL-6 induce the synthesis of the divalent metal transporter 1 and promote iron accumulation in neurons and microglia. Here, we review the recent literature on mitochondrial iron homeostasis and the role of inflammation on mitochondria dysfunction and iron accumulation on the neurodegenerative process that lead to cell death in Parkinson’s disease. We also put forward the hypothesis that mitochondrial dysfunction, iron accumulation and inflammation are part of a synergistic self-feeding cycle that ends in apoptotic cell death, once the antioxidant cellular defense systems are finally overwhelmed.

  19. Diurnal variations in brain iron concentrations in BXD RI mice.

    Science.gov (United States)

    Unger, E L; Jones, B C; Bianco, L E; Allen, R P; Earley, C J

    2014-03-28

    Under normal and dietary iron deficiency conditions, the BXD recombinant inbred (RI) strains of mice show large variations in regional brain iron concentration, particularly in the ventral midbrain (VMB). In a study utilizing just one of the BXD strains, diurnal changes in subregional brain iron concentration were found, which were dependent on the brain region and sex of the mice. The focus of this study was to determine if diurnal changes in VMB can be found across other BXD RI strains and whether a diurnal effect would be common to all strains or variable across strains similar to the large strain variability in iron concentrations determined during the first part of the light phase. Eight RI (BXD type) strains of mice of both sexes were selected for this study. Mice were sacrificed at postnatal day 120: half in the light phase (LP) and half in the dark phase (DP) of the light-dark cycle. Iron concentrations were determined in VMB, which was the primary region of interest, and five other brain regions. Exploratory analysis was also done on liver and spleen iron concentrations to assess for diurnal changes. Three strains showed clear diurnal variation in iron in the VMB and the others strains showed diurnal variations in other regions. These changes were not equally apparent in both sexes. Exploratory analysis also found strain×sex-dependent diurnal differences in spleen and liver iron. In conclusion, significant brain-regional-specific diurnal changes in total iron concentrations were found in a selection of BXD RI mice. Sex and strain are functional determinates of which regions will be affected and in what direction the affect will be. The study provides an animal model for future work into determining the biological and genetic basis of circadian influences on VMB iron homeostasis. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

  20. Visualizing Iron Deposition in Multiple Sclerosis Cadaver Brains

    Energy Technology Data Exchange (ETDEWEB)

    Habib, A.C.; Zheng, W.; Haacke, E.M.; Webb, S.; Nichol, H.; /SLAC

    2012-07-17

    To visualize and validate iron deposition in two cases of multiple sclerosis using rapid scanning X-Ray Fluorescence (RS-XRF) and Susceptibility Weighted Imaging (SWI). Two (2) coronal cadaver brain slices from patients clinically diagnosed with multiple sclerosis underwent magnetic resonance imaging (MRI), specifically SWI to image iron content. To confirm the presence of iron deposits and the absence of zinc-rich myelin in lesions, iron and zinc were mapped using RS-XRF. MS lesions were visualized using FLAIR and correlated with the absence of zinc by XRF. XRF and SWI showed that in the first MS case, there were large iron deposits proximal to the draining vein of the caudate nucleus as well as iron deposits associated with blood vessels throughout the globus pallidus. Less iron was seen in association with lesions than in the basal ganglia. The presence of larger amounts of iron correlated reasonably well between RS-XRF and SWI. In the second case, the basal ganglia appeared normal and acute perivascular iron deposition was absent. Perivascular iron deposition is seen in some but not all MS cases, giving credence to the use of SWI to assess iron involvement in MS pathology in vivo.

  1. Mutation in HFE gene decreases manganese accumulation and oxidative stress in the brain after olfactory manganese exposure.

    Science.gov (United States)

    Ye, Qi; Kim, Jonghan

    2016-06-01

    Increased accumulation of manganese (Mn) in the brain is significantly associated with neurobehavioral deficits and impaired brain function. Airborne Mn has a high systemic bioavailability and can be directly taken up into the brain, making it highly neurotoxic. While Mn transport is in part mediated by several iron transporters, the expression of these transporters is altered by the iron regulatory gene, HFE. Mutations in the HFE gene are the major cause of the iron overload disorder, hereditary hemochromatosis, one of the prevalent genetic diseases in humans. However, whether or not HFE mutation modifies Mn-induced neurotoxicity has not been evaluated. Therefore, our goal was to define the role of HFE mutation in Mn deposition in the brain and the resultant neurotoxic effects after olfactory Mn exposure. Mice carrying the H67D HFE mutation, which is homologous to the H63D mutation in humans, and their control, wild-type mice, were intranasally instilled with MnCl2 with different doses (0, 0.2, 1.0 and 5.0 mg kg(-1)) daily for 3 days. Mn levels in the blood, liver and brain were determined using inductively-coupled plasma mass spectrometry (ICP-MS). H67D mutant mice showed significantly lower Mn levels in the blood, liver, and most brain regions, especially in the striatum, while mice fed an iron-overload diet did not. Moreover, mRNA expression of ferroportin, an essential exporter of iron and Mn, was up-regulated in the striatum. In addition, the levels of isoprostane, a marker of lipid peroxidation, were increased in the striatum after Mn exposure in wild-type mice, but were unchanged in H67D mice. Together, our results suggest that the H67D mutation provides decreased susceptibility to Mn accumulation in the brain and neurotoxicity induced by inhaled Mn.

  2. Phytosiderophores determine thresholds for iron and zinc accumulation in biofortified rice endosperm while inhibiting the accumulation of cadmium.

    Science.gov (United States)

    Banakar, Raviraj; Alvarez Fernandez, Ana; Díaz-Benito, Pablo; Abadia, Javier; Capell, Teresa; Christou, Paul

    2017-10-13

    Nicotianamine (NA) and 2'-deoxymugenic acid (DMA) are metal-chelating ligands that promote the accumulation of metals in rice endosperm, but it is unclear how these phytosiderophores regulate the levels of different metals and limit their accumulation. In this study, transgenic rice plants producing high levels of NA and DMA accumulated up to 4-fold more iron (Fe) and 2-fold more zinc (Zn) in the endosperm compared with wild-type plants. The distribution of Fe and Zn in vegetative tissues suggested that both metals are sequestered as a buffering mechanism to avoid overloading the seeds. The buffering mechanism involves the modulation of genes encoding metal transporters in the roots and aboveground vegetative tissues. As well as accumulating more Fe and Zn, the endosperm of the transgenic plants accumulated less cadmium (Cd), suggesting that higher levels of Fe and Zn competitively inhibit Cd accumulation. Our data show that although there is a strict upper limit for Fe (~22.5 µg g-1 dry weight) and Zn (~84 µg g-1 dry weight) accumulation in the endosperm, the careful selection of strategies to increase endosperm loading with essential minerals can also limit the accumulation of toxic metals such as Cd, thus further increasing the nutritional value of rice. © The Author 2017. Published by Oxford University Press on behalf of the Society for Experimental Biology.

  3. Iron accumulation and dysregulation in the putamen in fragile X-associated tremor/ataxia syndrome.

    Science.gov (United States)

    Ariza, Jeanelle; Rogers, Hailee; Hartvigsen, Anna; Snell, Melissa; Dill, Michael; Judd, Derek; Hagerman, Paul; Martínez-Cerdeño, Verónica

    2017-04-01

    Fragile X-associated tremor/ataxia syndrome is an adult-onset disorder associated with premutation alleles of the FMR1 gene. This disorder is characterized by progressive action tremor, gait ataxia, and cognitive decline. Fragile X-associated tremor/ataxia syndrome pathology includes dystrophic white matter and intranuclear inclusions in neurons and astrocytes. We previously demonstrated that the transport of iron into the brain is altered in fragile X-associated tremor/ataxia syndrome; therefore, we also expect an alteration of iron metabolism in brain areas related to motor control. Iron is essential for cell metabolism, but uncomplexed iron leads to oxidative stress and contributes to the development of neurodegenerative diseases. We investigated a potential iron modification in the putamen - a structure that participates in motor learning and performance - in fragile X-associated tremor/ataxia syndrome. We used samples of putamen obtained from 9 fragile X-associated tremor/ataxia syndrome and 9 control cases to study iron localization using Perl's method, and iron-binding proteins using immunostaining. We found increased iron deposition in neuronal and glial cells in the putamen in fragile X-associated tremor/ataxia syndrome. We also found a generalized decrease in the amount of the iron-binding proteins transferrin and ceruloplasmin, and decreased number of neurons and glial cells that contained ceruloplasmin. However, we found increased levels of iron, transferrin, and ceruloplasmin in microglial cells, indicating an attempt by the immune system to remove the excess iron. Overall, found a deficit in proteins that eliminate extra iron from the cells with a concomitant increase in the deposit of cellular iron in the putamen in Fragile X-associated tremor/ataxia syndrome. © 2017 International Parkinson and Movement Disorder Society. © 2017 International Parkinson and Movement Disorder Society.

  4. Brain lipopigment accumulation in normal and pathological aging.

    Science.gov (United States)

    Riga, Dan; Riga, Sorin; Halalau, Florin; Schneider, Francisc

    2006-05-01

    A principal marker of brain vulnerability, stress, aging, and related pathology is represented by lipopigments (LPs)--lipofuscin, and ceroid. During ontogenesis, neuronal LP accumulations are significantly correlated with important changes in nerve cell morphology and biochemistry. In the aged neurons, LPs are present in all cellular compartments. Moreover, neuronal LP accumulations coexist with glial LP storage, especially in microglia. Owing to their transporting properties, and the migration capacity of microglia, glial cells deposit LP clusters in pericapillary areas. Thus, LP conglomerates appear in the whole nervous tissue, creating specific patterns of LP architectonics. Direct interrelations, critical LP concentrations, which generate cascades of negative subcellular events, and indirect impairment correlations determine characteristic neuropathologic aging profiles. These specific and associated negative neuropathologic consequences of LP accumulation have multiple and detrimental impacts on neuron and glia homeostasis, ranging from neuronal function to central nervous system physiology.

  5. Age-related accumulation of non-heme ferric and ferrous iron in mouse ovarian stroma visualized by sensitive non-heme iron histochemistry.

    Science.gov (United States)

    Asano, Yoshiya

    2012-03-01

    Sensitive non-heme iron histochemistry--namely, the perfusion-Perls method and perfusion-Turnbull method--was applied to study the distribution and age-related accumulation of non-heme ferric iron and ferrous iron in mouse ovary. Light and electron microscopic studies revealed that non-heme ferric iron is distributed predominantly in stromal tissue, especially in macrophages. By contrast, the distribution of non-heme ferrous iron was restricted to a few ovoid macrophages. Aged ovaries exhibited remarkable non-heme iron accumulation in all stromal cells. In particular, non-heme ferrous iron level was increased in stromal tissue, suggestive of increased levels of redox-active iron, which can promote oxidative stress. Moreover, intense localization of both non-heme ferric and ferrous iron was observed in aggregated large stromal cells that were then characterized as ceroid-laden enlarged macrophages with frothy cytoplasm. Intraperitoneal iron overload in adult mice resulted in non-heme iron deposition in the entire stroma and generation of enlarged macrophages, suggesting that excessive iron accumulation induced macrophage morphological changes. The data indicated that non-heme iron accumulation in ovarian stromal tissue may be related to aging of the ovary due to increasing oxidative stress.

  6. Exposure of aconitase to smoking-related oxidants results in iron loss and increased iron response protein-1 activity: potential mechanisms for iron accumulation in human arterial cells

    DEFF Research Database (Denmark)

    Talib, Jihan; Davies, Michael Jonathan

    2016-01-01

    Smokers have an elevated risk of cardiovascular disease, but the origin(s) of this increased risk are incompletely defined. Evidence supports an accumulation of the oxidant-generating enzyme myeloperoxidase (MPO) in the inflamed artery wall, and smokers have high levels of SCN−, a preferred MPO...... of the cytosolic isoform to iron response protein-1, which regulates intracellular iron levels. We show that exposure of isolated aconitase to increasing concentrations of HOSCN releases iron from the aconitase [Fe-S]4 cluster, and decreases enzyme activity. This is associated with protein thiol loss...... and modification of specific Cys residues in, and around, the [Fe-S]4 cluster. Exposure of HCAEC to HOSCN resulted in increased intracellular levels of chelatable iron, loss of aconitase activity and increased iron response protein-1 (IRP-1) activity. These data indicate HOSCN, an oxidant associated with oxidative...

  7. Legume seeds and cereal grains' capacity to accumulate iron while sprouting in order to obtain food fortificant.

    Science.gov (United States)

    Zielińska-Dawidziak, Magdalena; Staniek, Halina; Król, Ewelina; Piasecka-Kwiatkowska, Dorota; Twardowski, Tomasz

    2016-01-01

    Prepared sprouts, after culturing in a medium with an increased iron concentration, could become a beneficial food iron fortificant. However, the efficient iron accumulation depends on the plants genus, species and/or varieties. The aim of the study was to indicate the seeds or grains which accumulate iron most efficiently during the sprouting process. Alfalfa, lentil, lupine and soybean seeds as well as wheat grains were sprouted in abiotic stress conditions induced by the excess of iron(II) in culture media. The tolerance of these plants to iron concentration and its accumulation in the material obtained (with FAAS method) were analyzed. The smallest tolerance was noted for lentil seeds and wheat grains. Other plants developed in 25 mM solution of FeSO4. The highest accumulation of iron was observed in alfalfa sprouts. However, lupine and soybean seeds are the most recommended raw material for the production of the sprouts on an industrial scale.

  8. Copper Deficiency in Sheep with High Liver Iron Accumulation

    Directory of Open Access Journals (Sweden)

    Isadora Karolina Freitas de Sousa

    2012-01-01

    Full Text Available An outbreak of enzootic ataxia among sheep raised in the northeastern region of Brazil is described. Copper (Cu deficiency was diagnosed in a herd of 56 sheep, among which five presented characteristic clinical symptoms of enzootic ataxia. The symptoms began 30 days after birth, with a clinical condition that included locomotion difficulty, limb ataxia, tremors, and continual falls. Liver biopsies were performed and blood was collected to determine hepatic and plasmatic Cu, iron (Fe, and zinc (Zn concentration, respectively. The laboratory results showed that the animals presented low copper concentrations in the plasma and liver, without difference between the clinically healthy animals and those affected by enzootic ataxia. Even after supplementation with adequate Cu levels had been recommended, it was found on a new visit to the farm four months later that one animal still presented a clinical condition and that the hepatic Cu levels of the herd had not risen. Despite the low copper content of the diet, the high hepatic Fe levels found suggest that antagonism due to this element may have been an important factor in triggering copper deficiency in these animals, and thus, additional copper supplementation may be necessary for these animals.

  9. A novel approach to quantify different iron forms in ex-vivo human brain tissue

    Science.gov (United States)

    Kumar, Pravin; Bulk, Marjolein; Webb, Andrew; van der Weerd, Louise; Oosterkamp, Tjerk H.; Huber, Martina; Bossoni, Lucia

    2016-12-01

    We propose a novel combination of methods to study the physical properties of ferric ions and iron-oxide nanoparticles in post-mortem human brain, based on the combination of Electron Paramagnetic Resonance (EPR) and SQUID magnetometry. By means of EPR, we derive the concentration of the low molecular weight iron pool, as well as the product of its electron spin relaxation times. Additionally, by SQUID magnetometry we identify iron mineralization products ascribable to a magnetite/maghemite phase and a ferrihydrite (ferritin) phase. We further derive the concentration of magnetite/maghemite and of ferritin nanoparticles. To test out the new combined methodology, we studied brain tissue of an Alzheimer’s patient and a healthy control. Finally, we estimate that the size of the magnetite/maghemite nanoparticles, whose magnetic moments are blocked at room temperature, exceeds 40-50 nm, which is not compatible with the ferritin protein, the core of which is typically 6-8 nm. We believe that this methodology could be beneficial in the study of neurodegenerative diseases such as Alzheimer’s Disease which are characterized by abnormal iron accumulation in the brain.

  10. Iron accumulation in the substantia nigra of patients with Alzheimer disease and parkinsonism.

    Science.gov (United States)

    Brar, Sonia; Henderson, David; Schenck, John; Zimmerman, Earl A

    2009-03-01

    Preliminary studies have shown an increase in iron accumulation in the substantia nigra but not in the hippocampus in patients with Parkinson disease without dementia and the reverse in patients with Alzheimer disease (AD) and no parkinsonism. To determine whether iron levels (measured as T2 shortening on magnetic resonance images) are greater in the substantia nigra of patients with AD who have parkinsonism than in those with AD alone. Case-control study. Albany Medical College, Albany, New York. Fifteen patients with only AD (controls) and 18 with AD as well as parkinsonism, aged 56 to 89 years, and with a total Clinical Dementia Rating of 5.0 to 11.5. Patients were selected according to the purity of their disease; patients with a Unified Parkinson's Disease Rating Scale motor score of 15 or greater were considered to have parkinsonism. Main Outcome Measure Area under the curve for short T2 (30 milliseconds) in patients with only AD vs patients with AD who developed parkinsonism. Patients who developed parkinsonism along with their existing dementia had significantly more iron in their substantia nigra than did patients with AD alone (P = .03, 2-sample t test). Iron accumulation may be a predictor of parkinsonism. The development of parkinsonism during the course of AD appears to be associated with the accumulation of iron, which in turn may contribute to the pathogenesis of neurologic decline.

  11. Abnormal brain iron homeostasis in human and animal prion disorders

    National Research Council Canada - National Science Library

    Singh, Ajay; Isaac, Alfred Orina; Luo, Xiu; Mohan, Maradumane L; Cohen, Mark L; Chen, Fusong; Kong, Qingzhong; Bartz, Jason; Singh, Neena

    2009-01-01

    ...)), a beta-sheet rich isoform of a normal cell-surface glycoprotein, the prion protein (PrP(C)). Limited reports suggest imbalance of brain iron homeostasis as a significant associated cause of neurotoxicity in prion-infected cell and mouse models...

  12. Mitochondrial iron accumulation exacerbates hepatic toxicity caused by hepatitis C virus core protein

    Energy Technology Data Exchange (ETDEWEB)

    Sekine, Shuichi; Ito, Konomi; Watanabe, Haruna; Nakano, Takafumi [Laboratory of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8675 (Japan); Moriya, Kyoji; Shintani, Yoshizumi; Fujie, Hajime; Tsutsumi, Takeya; Miyoshi, Hideyuki; Fujinaga, Hidetake; Shinzawa, Seiko; Koike, Kazuhiko [Department of Internal Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655 (Japan); Horie, Toshiharu, E-mail: t.horie@thu.ac.jp [Laboratory of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8675 (Japan)

    2015-02-01

    Patients with long-lasting hepatitis C virus (HCV) infection are at major risk of hepatocellular carcinoma (HCC). Iron accumulation in the livers of these patients is thought to exacerbate conditions of oxidative stress. Transgenic mice that express the HCV core protein develop HCC after the steatosis stage and produce an excess of hepatic reactive oxygen species (ROS). The overproduction of ROS in the liver is the net result of HCV core protein-induced dysfunction of the mitochondrial respiratory chain. This study examined the impact of ferric nitrilacetic acid (Fe-NTA)-mediated iron overload on mitochondrial damage and ROS production in HCV core protein-expressing HepG2 (human HCC) cells (Hep39b cells). A decrease in mitochondrial membrane potential and ROS production were observed following Fe-NTA treatment. After continuous exposure to Fe-NTA for six days, cell toxicity was observed in Hep39b cells, but not in mock (vector-transfected) HepG2 cells. Moreover, mitochondrial iron ({sup 59}Fe) uptake was increased in the livers of HCV core protein-expressing transgenic mice. This increase in mitochondrial iron uptake was inhibited by Ru360, a mitochondrial Ca{sup 2+} uniporter inhibitor. Furthermore, the Fe-NTA-induced augmentation of mitochondrial dysfunction, ROS production, and cell toxicity were also inhibited by Ru360 in Hep39b cells. Taken together, these results indicate that Ca{sup 2+} uniporter-mediated mitochondrial accumulation of iron exacerbates hepatocyte toxicity caused by the HCV core protein. - Highlights: • Iron accumulation in the livers of patients with hepatitis C virus (HCV) infection is thought to exacerbate oxidative stress. • The impact of iron overload on mitochondrial damage and ROS production in HCV core protein-expressing cells were examined. • Mitochondrial iron uptake was increased in the livers of HCV core protein-expressing transgenic mice. • Ca{sup 2+} uniporter-mediated mitochondrial accumulation of iron exacerbates

  13. Myricetin ameliorates scopolamine-induced memory impairment in mice via inhibiting acetylcholinesterase and down-regulating brain iron.

    Science.gov (United States)

    Wang, Beiyun; Zhong, Yuan; Gao, Chengjie; Li, Jingbo

    2017-08-19

    The aim of our study was to investigate to investigate the effect of myricetin on Alzheimer's disease (AD) and its underlying mechanisms. In our study, Myricetin effectively attenuated Fe(2+)-induced cell death in SH-SY5Y cells in vitro. In a mouse model of AD, myricetin treatment significantly reversed scopolamine-induced cognitive deficits deriving from a novel action of inhibiting acetylcholinesterase (AChE) and down-regulating brain iron. Furthermore, Myricetin treatment reduced oxidative damage and increased antioxidant enzymes activity in mice. Interestingly, the effect of myricetin was largely abolished by high iron diet. Therefore we suggested that treatment with myricetin attenuated cognitive deficits in mice via inhibiting AChE and brain iron regulation. In addition, myricetin reduce iron contents may via inhibiting transferrin receptor 1 (TrR1) expression. In conclusion, accumulated data demonstrates that myricetin is a potential multifunctional drug for AD. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Iron accumulation in deep cortical layers accounts for MRI signal abnormalities in ALS: correlating 7 tesla MRI and pathology.

    Directory of Open Access Journals (Sweden)

    Justin Y Kwan

    Full Text Available Amyotrophic lateral sclerosis (ALS is a progressive neurodegenerative disorder characterized by cortical and spinal motor neuron dysfunction. Routine magnetic resonance imaging (MRI studies have previously shown hypointense signal in the motor cortex on T(2-weighted images in some ALS patients, however, the cause of this finding is unknown. To investigate the utility of this MR signal change as a marker of cortical motor neuron degeneration, signal abnormalities on 3T and 7T MR images of the brain were compared, and pathology was obtained in two ALS patients to determine the origin of the motor cortex hypointensity. Nineteen patients with clinically probable or definite ALS by El Escorial criteria and 19 healthy controls underwent 3T MRI. A 7T MRI scan was carried out on five ALS patients who had motor cortex hypointensity on the 3T FLAIR sequence and on three healthy controls. Postmortem 7T MRI of the brain was performed in one ALS patient and histological studies of the brains and spinal cords were obtained post-mortem in two patients. The motor cortex hypointensity on 3T FLAIR images was present in greater frequency in ALS patients. Increased hypointensity correlated with greater severity of upper motor neuron impairment. Analysis of 7T T(2(*-weighted gradient echo imaging localized the signal alteration to the deeper layers of the motor cortex in both ALS patients. Pathological studies showed increased iron accumulation in microglial cells in areas corresponding to the location of the signal changes on the 3T and 7T MRI of the motor cortex. These findings indicate that the motor cortex hypointensity on 3T MRI FLAIR images in ALS is due to increased iron accumulation by microglia.

  15. Role of transferrin receptor 2 in hepatic accumulation of iron in patients with chronic hepatitis C.

    Science.gov (United States)

    Mifuji, Rumi; Kobayashi, Yoshinao; Ma, Ning; Qiang, Qin Li; Urawa, Naohito; Horiike, Shinichiro; Iwasa, Motoh; Kaito, Masahiko; Malavasi, Fabio; Adachi, Yukihiko

    2006-01-01

    Iron deposition in the liver is a common finding in patients with chronic hepatitis C (CH-C). The mechanism of this hepatic accumulation of iron is not completely understood. This study assessed if the protein expression of transferrin receptor 2 (TfR2) is upregulated in the liver of patients with CH-C and if TfR2 protein mediates iron accumulation during hepatitis C virus (HCV) infection. Liver specimens from patients with CH-C that underwent interferon (IFN) therapy (n=23) and from patients with CH-B (n=18) were evaluated. Hepatic expression of TfR2 protein was analyzed by immunohistochemistry. Total hepatic iron score (THIS) was evaluated by Prussian blue staining. TfR2 protein was expressed in the cell membrane and cytosol of hepatocytes. Cytosol TfR2 protein was found to co-localize with Tf. THIS (P=0.0198) and hepatic TfR2 (P=0.0047) expression were significantly higher in CH-C than in CH-B. The change in THIS values (rho=0.580, P=0.0079) and the grade of histological activity (rho=0.444, P=0.0373) were significantly correlated with changes in TfR2 expression after IFN therapy. The protein expression of TfR2 is significantly associated with iron deposition in the liver in patients with CH-C. HCV infection may affect the hepatic expression of TfR2, leading to iron accumulation in the liver.

  16. Cp/Heph mutant mice have iron-induced neurodegeneration diminished by deferiprone

    Science.gov (United States)

    Zhao, Liangliang; Hadziahmetovic, Majda; Wang, Chenguang; Xu, Xueying; Song, Ying; Jinnah, H.A.; Wodzinska, Jolanta; Iacovelli, Jared; Wolkow, Natalie; Krajacic, Predrag; Weissberger, Alyssa Cwanger; Connelly, John; Spino, Michael; Lee, Michael K.; Connor, James; Giasson, Benoit; Harris, Z. Leah; Dunaief, Joshua L.

    2016-01-01

    Brain iron accumulates in several neurodegenerative diseases and can cause oxidative damage, but mechanisms of brain iron homeostasis are incompletely understood. Patients with mutations in the cellular iron-exporting ferroxidase ceruloplasmin (Cp) have brain iron accumulation causing neurodegeneration. Here, we assessed the brains of mice with combined mutation of Cp and its homolog hephaestin. Compared to single mutants, brain iron accumulation was accelerated in double mutants in the cerebellum, substantia nigra, and hippocampus. Iron accumulated within glia, while neurons were iron deficient. There was loss of both neurons and glia. Mice developed ataxia and tremor, and most died by 9 months. Treatment with the oral iron chelator deferiprone diminished brain iron levels, protected against neuron loss, and extended lifespan. Ferroxidases play important, partially overlapping roles in brain iron homeostasis by facilitating iron export from glia, making iron available to neurons. PMID:26303407

  17. Expression of iron-related genes in human brain and brain tumors

    Directory of Open Access Journals (Sweden)

    Britton Robert S

    2009-04-01

    Full Text Available Abstract Background Defective iron homeostasis may be involved in the development of some diseases within the central nervous system. Although the expression of genes involved in normal iron balance has been intensively studied in other tissues, little is known about their expression in the brain. We investigated the mRNA levels of hepcidin (HAMP, HFE, neogenin (NEO1, transferrin receptor 1 (TFRC, transferrin receptor 2 (TFR2, and hemojuvelin (HFE2 in normal human brain, brain tumors, and astrocytoma cell lines. The specimens included 5 normal brain tissue samples, 4 meningiomas, one medulloblastoma, 3 oligodendrocytic gliomas, 2 oligoastrocytic gliomas, 8 astrocytic gliomas, and 3 astrocytoma cell lines. Results Except for hemojuvelin, all genes studied had detectable levels of mRNA. In most tumor types, the pattern of gene expression was diverse. Notable findings include high expression of transferrin receptor 1 in the hippocampus and medulla oblongata compared to other brain regions, low expression of HFE in normal brain with elevated HFE expression in meningiomas, and absence of hepcidin mRNA in astrocytoma cell lines despite expression in normal brain and tumor specimens. Conclusion These results indicate that several iron-related genes are expressed in normal brain, and that their expression may be dysregulated in brain tumors.

  18. Acetamiprid Accumulates in Different Amounts in Murine Brain Regions

    Directory of Open Access Journals (Sweden)

    Hayato Terayama

    2016-09-01

    Full Text Available Neonicotinoids such as acetamiprid (ACE belong to a new and widely used single class of pesticides. Neonicotinoids mimic the chemical structure of nicotine and share agonist activity with the nicotine acetylcholine receptor (nAchR. Neonicotinoids are widely considered to be safe in humans; however, they have recently been implicated in a number of human health disorders. A wide range of musculoskeletal and neuromuscular disorders associated with high doses of neonicotinoids administered to animals have also been reported. Consequently, we used a mouse model to investigate the response of the central nervous system to ACE treatment. Our results show that exposure to ACE-containing water for three or seven days (decuple and centuple of no observable adverse effect level (NOAEL/day caused a decrease in body weight in 10-week old A/JJmsSlc (A/J mice. However, the treatments did not affect brain histology or expression of CD34. ACE concentrations were significantly higher in the midbrain of ACE-treated mice than that of the normal and vehicle groups. Expression levels of α7, α4, and β2 nAChRs were found to be low in the olfactory bulb and midbrain of normal mice. Furthermore, in the experimental group (centuple ACE-containing water for seven days, β2 nAChR expression decreased in many brain regions. Information regarding the amount of accumulated ACE and expression levels of the acetylcholine receptor in each region of the brain is important for understanding any clinical symptoms that may be associated with ACE exposure.

  19. Size-Dependent Accumulation of PEGylated Silane-Coated Magnetic Iron Oxide Nanoparticles in Murine Tumors

    DEFF Research Database (Denmark)

    Larsen, Esben Kjær Unmack; Nielsen, T.; Wittenborn, T.

    2009-01-01

    Magnetic nanoparticles (MNP) can be used as contrast-enhancing agents to visualize tumors by magnetic resonance imaging (MRI). Here we describe an easy synthesis method of magnetic nanoparticles coated with polyethylene glycol (PEG) and demonstrate size-dependent accumulation in murine tumors...... following intravenous injection. Biocompatible iron oxide MNPs coated with PEG were prepared by replacing oleic acid with a biocompatible and commercially available silane-PEG to provide an easy and effective method for chemical coating. The colloidal stable PEGylated MNPs were magnetically separated...... into two distinct size subpopulations of 20 and 40 nm mean diameters with increased phagocytic uptake observed for the 40 nm size range in vitro. MRI detection revealed greater iron accumulation in murine tumors for 40 nm nanoparticles after intravenous injection. The enhanced MRI contrast of the larger...

  20. Variation and inheritance of iron reductase activity in the roots of common bean (Phaseolus vulgaris L. and association with seed iron accumulation QTL

    Directory of Open Access Journals (Sweden)

    Fernandez Andrea C

    2010-10-01

    Full Text Available Abstract Background Iron deficiency anemia is a global problem which often affects women and children of developing countries. Strategy I plants, such as common bean (Phaseolus vulgaris L. take up iron through a process that involves an iron reduction mechanism in their roots; this reduction is required to convert ferric iron to ferrous iron. Root absorbed iron is critical for the iron nutrition of the plant, and for the delivery of iron to the shoot and ultimately the seeds. The objectives of this study were to determine the variability and inheritance for iron reductase activity in a range of genotypes and in a low × high seed iron cross (DOR364 × G19833, to identify quantitative trait loci (QTL for this trait, and to assess possible associations with seed iron levels. Results The experiments were carried out with hydroponically grown plants provided different amounts of iron varying between 0 and 20 μM Fe(III-EDDHA. The parents, DOR364 and G19833, plus 13 other cultivated or wild beans, were found to differ in iron reductase activity. Based on these initial experiments, two growth conditions (iron limited and iron sufficient were selected as treatments for evaluating the DOR364 × G19833 recombinant inbred lines. A single major QTL was found for iron reductase activity under iron-limited conditions (1 μM Fe on linkage group b02 and another major QTL was found under iron sufficient conditions (15 μM Fe on linkage group b11. Associations between the b11 QTL were found with several QTL for seed iron. Conclusions Genes conditioning iron reductase activity in iron sufficient bean plants appear to be associated with genes contributing to seed iron accumulation. Markers for bean iron reductase (FRO homologues were found with in silico mapping based on common bean synteny with soybean and Medicago truncatula on b06 and b07; however, neither locus aligned with the QTL for iron reductase activity. In summary, the QTL for iron reductase activity

  1. Mini-review: The Morphology, Mineralogy and Microbiology of Accumulated Iron Corrosion Products

    Science.gov (United States)

    2014-03-11

    RESPONSIBLE PERSON 19b. TELEPHONE NUMBER (Include area code) 11-03-2014 Journal Article Mini-review: the morphology, mineralogy and microbiology of...d Mini-review: the morphology, mineralogy and microbiology of accumulated iron corrosion products Brenda J. Littlea*, Tammie L. Gerkeb and Jason S...Leea aNaval Research Laboratory, Stennis Space Center, MS, USA; bDepartment of Geology and Environmental Earth Science, Miami University, Middletown

  2. Magnetic Deposits of Iron Oxides in the Human Brain

    Directory of Open Access Journals (Sweden)

    Makohusová Miroslava

    2014-06-01

    Full Text Available Deposits of iron oxides in the human brain (globus pallidus are visible under electron microscopy as object of regular and or/irregular shape but giving sharp diffraction patterns in the transmission mode. The SQUID magnetometry reveals that the magnetization curves decline form an ideal Langevin function due to the dominating diamagnetism of organic tissue. The fitting procedure yields the quantitative characteristics of the overall magnetization curves that were further processed by statistical multivariate methods

  3. Iron-Restricted Diet Affects Brain Ferritin Levels, Dopamine Metabolism and Cellular Prion Protein in a Region-Specific Manner

    Science.gov (United States)

    Pino, Jessica M. V.; da Luz, Marcio H. M.; Antunes, Hanna K. M.; Giampá, Sara Q. de Campos; Martins, Vilma R.; Lee, Kil S.

    2017-01-01

    Iron is an essential micronutrient for several physiological functions, including the regulation of dopaminergic neurotransmission. On the other hand, both iron, and dopamine can affect the folding and aggregation of proteins related with neurodegenerative diseases, such as cellular prion protein (PrPC) and α-synuclein, suggesting that deregulation of iron homeostasis and the consequential disturbance of dopamine metabolism can be a risk factor for conformational diseases. These proteins, in turn, are known to participate in the regulation of iron and dopamine metabolism. In this study, we evaluated the effects of dietary iron restriction on brain ferritin levels, dopamine metabolism, and the expression levels of PrPC and α-synuclein. To achieve this goal, C57BL/6 mice were fed with iron restricted diet (IR) or with normal diet (CTL) for 1 month. IR reduced iron and ferritin levels in liver. Ferritin reduction was also observed in the hippocampus. However, in the striatum of IR group, ferritin level was increased, suggesting that under iron-deficient condition, each brain area might acquire distinct capacity to store iron. Increased lipid peroxidation was observed only in hippocampus of IR group, where ferritin level was reduced. IR also generated discrete results regarding dopamine metabolism of distinct brain regions: in striatum, the level of dopamine metabolites (DOPAC and HVA) was reduced; in prefrontal cortex, only HVA was increased along with the enhanced MAO-A activity; in hippocampus, no alterations were observed. PrPC levels were increased only in the striatum of IR group, where ferritin level was also increased. PrPC is known to play roles in iron uptake. Thus, the increase of PrPC in striatum of IR group might be related to the increased ferritin level. α-synuclein was not altered in any regions. Abnormal accumulation of ferritin, increased MAO-A activity or lipid peroxidation are molecular features observed in several neurological disorders. Our

  4. Iron-Restricted Diet Affects Brain Ferritin Levels, Dopamine Metabolism and Cellular Prion Protein in a Region-Specific Manner

    Directory of Open Access Journals (Sweden)

    Jessica M. V. Pino

    2017-05-01

    Full Text Available Iron is an essential micronutrient for several physiological functions, including the regulation of dopaminergic neurotransmission. On the other hand, both iron, and dopamine can affect the folding and aggregation of proteins related with neurodegenerative diseases, such as cellular prion protein (PrPC and α-synuclein, suggesting that deregulation of iron homeostasis and the consequential disturbance of dopamine metabolism can be a risk factor for conformational diseases. These proteins, in turn, are known to participate in the regulation of iron and dopamine metabolism. In this study, we evaluated the effects of dietary iron restriction on brain ferritin levels, dopamine metabolism, and the expression levels of PrPC and α-synuclein. To achieve this goal, C57BL/6 mice were fed with iron restricted diet (IR or with normal diet (CTL for 1 month. IR reduced iron and ferritin levels in liver. Ferritin reduction was also observed in the hippocampus. However, in the striatum of IR group, ferritin level was increased, suggesting that under iron-deficient condition, each brain area might acquire distinct capacity to store iron. Increased lipid peroxidation was observed only in hippocampus of IR group, where ferritin level was reduced. IR also generated discrete results regarding dopamine metabolism of distinct brain regions: in striatum, the level of dopamine metabolites (DOPAC and HVA was reduced; in prefrontal cortex, only HVA was increased along with the enhanced MAO-A activity; in hippocampus, no alterations were observed. PrPC levels were increased only in the striatum of IR group, where ferritin level was also increased. PrPC is known to play roles in iron uptake. Thus, the increase of PrPC in striatum of IR group might be related to the increased ferritin level. α-synuclein was not altered in any regions. Abnormal accumulation of ferritin, increased MAO-A activity or lipid peroxidation are molecular features observed in several neurological

  5. Accumulation and distribution of iron, cadmium, lead and nickel in cucumber plants grown in hydroponics containing two different chelated iron supplies.

    Science.gov (United States)

    Csog, Árpád; Mihucz, Victor G; Tatár, Eniko; Fodor, Ferenc; Virág, István; Majdik, Cornelia; Záray, Gyula

    2011-07-01

    Cucumber plants grown in hydroponics containing 10 μM Cd(II), Ni(II) and Pb(II), and iron supplied as Fe(III) EDTA or Fe(III) citrate in identical concentrations, were investigated by total-reflection X-ray fluorescence spectrometry with special emphasis on the determination of iron accumulation and distribution within the different plant compartments (root, stem, cotyledon and leaves). The extent of Cd, Ni and Pb accumulation and distribution were also determined. Generally, iron and heavy-metal contaminant accumulation was higher when Fe(III) citrate was used. The accumulation of nickel and lead was higher by about 20% and 100%, respectively, if the iron supply was Fe(III) citrate. The accumulation of Cd was similar. In the case of Fe(III) citrate, the total amounts of Fe taken up were similar in the control and heavy-metal-treated plants (27-31 μmol/plant). Further, the amounts of iron transported from the root towards the shoot of the control, lead- and nickel-contaminated plants were independent of the iron(III) form. Although Fe mobility could be characterized as being low, its distribution within the shoot was not significantly affected by the heavy metals investigated. Copyright © 2011 Elsevier GmbH. All rights reserved.

  6. Implication of eolian delivery and accumulation of highly reactive iron to the Atlantic Ocean

    Science.gov (United States)

    Lee, B. K.; Owens, J. D.; Lyons, T. W.

    2014-12-01

    Iron, although abundant in the Earth's crust, is present at low concentrations in sea water and is a limiting nutrient for phytoplankton. Eolian dust (loess) is a major source of this micronutrient, and its deposition has important implications for the global CO2 budget. In this study, we explore distributions of potentially bioreactive Fe, the soluble fraction required by phytoplankton for photosynthesis and nitrogen assimilation, in deep-sea sediments in the North and South Atlantic Oceans. We used a state-of-the-art Fe speciation technique to characterize Fe inputs from different source regions, specifically North Africa and Patagonia to address the patterns and implications across glacial-interglacial time scales. In many open-ocean regions the input of new iron to the surface waters is dominated by the atmospheric deposition of soluble iron in eolian dusts. Multiple records have shown dust accumulation is correlated with glacial-interglacial cycles - glacial periods are substantially dustier. Furthermore, the delivery of eolian dust to the North and South Atlantic Oceans are from two very different source regions and soil types. We analyzed IODP cores from these two regions and our preliminary data shows similar pattern of iron distribution from both the North and South Atlantic Oceans. To date we have found no simple global pattern of bioavailable iron distribution during glacial and interglacial periods. We have analyzed a range of size distributions to isolate the dust-dominated fraction and the data shows no size effects in bioavailable form of iron distribution. We will explore the role of deep-water dust dissolution and sedimentary redox implications and its role on the bioreactive Fe record in marine cores.

  7. Accumulation of iron and arsenic in the Chandina alluvium of the lower delta plain, Southeastern Bangladesh

    Science.gov (United States)

    Zahid, A.; Hassan, M.Q.; Breit, G.N.; Balke, K.-D.; Flegr, M.

    2009-01-01

    Accumulations of iron, manganese, and arsenic occur in the Chandina alluvium of southeastern Bangladesh within 2.5 m of the ground surface. These distinctive orange-brown horizons are subhorizontal and consistently occur within 1 m of the contact of the aerated (yellow-brown) and water-saturated (gray) sediment. Ferric oxyhydroxide precipitates that define the horizons form by oxidation of reduced iron in pore waters near the top of the saturated zone when exposed to air in the unsaturated sediment. Hydrous Fe-oxide has a high specific surface area and thus a high adsorption capacity that absorbs the bulk of arsenic also present in the reduced pore water, resulting in accumulations containing as much as 280 ppm arsenic. The steep redox gradient that characterizes the transition of saturated and unsaturated sediment also favors accumulation of manganese oxides in the oxidized sediment. Anomalous concentrations of phosphate and molybdenum also detected in the ferric oxyhydroxide-enriched sediment are attributed to sorption processes. ?? Springer Science+Business Media B.V. 2008.

  8. Iron-related gene variants and brain iron in multiple sclerosis and healthy individuals.

    Science.gov (United States)

    Hagemeier, Jesper; Ramanathan, Murali; Schweser, Ferdinand; Dwyer, Michael G; Lin, Fuchun; Bergsland, Niels; Weinstock-Guttman, Bianca; Zivadinov, Robert

    2018-01-01

    Brain iron homeostasis is known to be disturbed in multiple sclerosis (MS), yet little is known about the association of common gene variants linked to iron regulation and pathological tissue changes in the brain. In this study, we investigated the association of genetic determinants linked to iron regulation with deep gray matter (GM) magnetic susceptibility in both healthy controls (HC) and MS patients. Four hundred (400) patients with MS and 150 age- and sex-matched HCs were enrolled and obtained 3 T MRI examination. Three (3) single nucleotide polymorphisms (SNPs) associated with iron regulation were genotyped: two SNPs in the human hereditary hemochromatosis protein gene HFE : rs1800562 (C282Y mutation) and rs1799945 (H63D mutation), as well as the rs1049296 SNP in the transferrin gene (C2 mutation). The effects of disease and genetic status were studied using quantitative susceptibility mapping (QSM) voxel-based analysis (VBA) and region-of-interest (ROI) analysis of the deep GM. The general linear model framework was used to compare groups. Analyses were corrected for age and sex, and adjusted for false discovery rate. We found moderate increases in susceptibility in the right putamen of participants with the C282Y (+ 6.1 ppb) and H63D (+ 6.9 ppb) gene variants vs. non-carriers, as well as a decrease in thalamic susceptibility of progressive MS patients with the C282Y mutation (left: - 5.3 ppb, right: - 6.7 ppb, p < 0.05). Female MS patients had lower susceptibility in the caudate (- 6.0 ppb) and putamen (left: - 3.9 ppb, right: - 4.6 ppb) than men, but only when they had a wild-type allele (p < 0.05). Iron-gene linked increases in putamen susceptibility (in HC and relapsing remitting MS) and decreases in thalamus susceptibility (in progressive MS), coupled with apparent sex interactions, indicate that brain iron in healthy and disease states may be influenced by genetic factors.

  9. Evaluation of constitutive iron reductase (AtFRO2 expression on mineral accumulation and distribution in soybean (Glycine max. L

    Directory of Open Access Journals (Sweden)

    Marta Wilton Vasconcelos

    2014-04-01

    Full Text Available Iron is an important micronutrient in human and plant nutrition. Adequate iron nutrition during crop production is central for assuring appropriate iron concentrations in the harvestable organs, for human food or animal feed. The whole-plant movement of iron involves several processes, including the reduction of ferric to ferrous iron at several locations throughout the plant, prior to transmembrane trafficking of ferrous iron. In this study, soybean plants that constitutively expressed the AtFRO2 iron reductase gene were analyzed for leaf iron reductase activity, as well as the effect of this transgene's expression on root, leaf, pod wall, and seed mineral concentrations. High Fe supply, in combination with the constitutive expression of AtFRO2, resulted in significantly higher concentrations of different minerals in roots (K, P, Zn, Ca, Ni, Mg and Mo, pod walls (Fe, K, P, Cu and Ni, leaves (Fe, P, Cu, Ca, Ni and Mg and seeds (Fe, Zn, Cu and Ni. Leaf and pod wall iron concentrations increased as much as 500% in transgenic plants, while seed iron concentrations only increased by 10%, suggesting that factors other than leaf and pod wall reductase activity were limiting the translocation of iron to seeds. Protoplasts isolated from transgenic leaves had three-fold higher reductase activity than controls. Expression levels of the iron storage protein, ferritin, were higher in the transgenic leaves than in wild-type, suggesting that the excess iron may be stored as ferritin in the leaves and therefore unavailable for phloem loading and delivery to the seeds. Also, citrate and malate levels in the roots and leaves of transgenic plants were significantly higher than in wild-type, suggesting that organic acid production could be related to the increased accumulation of minerals in roots, leaves and pod walls, but not in the seeds. All together, these results suggest a more ubiquitous role for the iron reductase in whole-plant mineral accumulation and

  10. Possible link between Hg and Cd accumulation in the brain of long-finned pilot whales (Globicephala melas)

    Energy Technology Data Exchange (ETDEWEB)

    Gajdosechova, Zuzana [Trace Element Speciation Laboratory, Department of Chemistry, Meston Walk, University of Aberdeen, Aberdeen AB24 3UE (United Kingdom); Brownlow, Andrew [SAC Wildlife Unit, Inverness (United Kingdom); Cottin, Nicolas T.; Fernandes, Mariana [Trace Element Speciation Laboratory, Department of Chemistry, Meston Walk, University of Aberdeen, Aberdeen AB24 3UE (United Kingdom); Read, Fiona L. [Oceanlab, University of Aberdeen, Main Street, Newburgh AB41 6AA (United Kingdom); Urgast, Dagmar S.; Raab, Andrea; Feldmann, Jörg; Krupp, Eva M. [Trace Element Speciation Laboratory, Department of Chemistry, Meston Walk, University of Aberdeen, Aberdeen AB24 3UE (United Kingdom)

    2016-03-01

    The bioaccumulation of metals was investigated by analysis of liver, kidney, muscle and brain tissue of a pod of 21 long-finned pilot whales (Globicephala melas) of all ages stranded in Scotland, UK. The results are the first to report cadmium (Cd) passage through the blood–brain barrier of pilot whales and provide a comprehensive study of the long-term (up to 35 years) mammalian exposure to the environmental pollutants. Additionally, linear accumulation of mercury (Hg) was observed in all studied tissues, whereas for Cd this was only observed in the liver. Total Hg concentration above the upper neurochemical threshold was found in the sub-adult and adult brains and methylmercury (MeHg) of 2.2 mg/kg was found in the brain of one individual. Inter-elemental analysis showed significant positive correlations of Hg with selenium (Se) and Cd with Se in all studied tissues. Furthermore, differences in the elemental concentrations in the liver and brain tissues were found between juvenile, sub-adult and adult groups. The highest concentrations of manganese, iron, zinc, Se, Hg and MeHg were noted in the livers, whereas Cd predominantly accumulated in the kidneys. High concentrations of Hg and Cd in the tissues of pilot whales presented in this study reflect ever increasing toxic stress on marine mammals. - Highlights: • Trace elements were measured in a pod of 21 pilot whales stranded in Scotland. • Bioaccumulation of mercury and methyl mercury was found in all studied tissues. • Cadmium age related accumulation was observed in the liver and brain tissues. • Cadmium-selenium correlations suggest formation of cadmium-selenium complexes.

  11. Cell wall targeted in planta iron accumulation enhances biomass conversion and seed iron concentration in Arabidopsis and rice

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Haibing [Center for Direct Catalytic Conversion Of Biomass to Biofuels (C3Bio), Purdue University, West Lafayette IN USA; Department of Horticulture, Purdue University, West Lafayette IN USA; Department of Biological Sciences, Purdue University, West Lafayette IN USA; Wei, Hui [Biosciences Center, National Renewable Energy Laboratory, Golden CO USA; Ma, Guojie [Center for Direct Catalytic Conversion Of Biomass to Biofuels (C3Bio), Purdue University, West Lafayette IN USA; Department of Horticulture, Purdue University, West Lafayette IN USA; Antunes, Mauricio S. [Center for Direct Catalytic Conversion Of Biomass to Biofuels (C3Bio), Purdue University, West Lafayette IN USA; Department of Biological Sciences, Purdue University, West Lafayette IN USA; Vogt, Stefan [X-ray Science Division, Advanced Photon Source, Argonne National Laboratory, Argonne IL USA; Cox, Joseph [Center for Direct Catalytic Conversion Of Biomass to Biofuels (C3Bio), Purdue University, West Lafayette IN USA; Department of Horticulture, Purdue University, West Lafayette IN USA; Zhang, Xiao [Department of Horticulture, Purdue University, West Lafayette IN USA; Liu, Xiping [Center for Direct Catalytic Conversion Of Biomass to Biofuels (C3Bio), Purdue University, West Lafayette IN USA; Department of Horticulture, Purdue University, West Lafayette IN USA; Bu, Lintao [National Bioenergy Center, National Renewable Energy Laboratory, Golden CO USA; Gleber, S. Charlotte [X-ray Science Division, Advanced Photon Source, Argonne National Laboratory, Argonne IL USA; Carpita, Nicholas C. [Department of Biological Sciences, Purdue University, West Lafayette IN USA; Department of Botany and Plant Pathology, Purdue University, West Lafayette IN USA; Makowski, Lee [Department of Bioengineering, Northeastern University, Boston MA USA; Department of Chemistry and Chemical Biology, Northeastern University, Boston MA USA; Himmel, Michael E. [Biosciences Center, National Renewable Energy Laboratory, Golden CO USA; Tucker, Melvin P. [X-ray Science Division, Advanced Photon Source, Argonne National Laboratory, Argonne IL USA; McCann, Maureen C. [Center for Direct Catalytic Conversion Of Biomass to Biofuels (C3Bio), Purdue University, West Lafayette IN USA; Department of Biological Sciences, Purdue University, West Lafayette IN USA; Murphy, Angus S. [Center for Direct Catalytic Conversion Of Biomass to Biofuels (C3Bio), Purdue University, West Lafayette IN USA; Department of Horticulture, Purdue University, West Lafayette IN USA; Department of Plant Science and Landscape Architecture, University of Maryland, College Park MD USA; Peer, Wendy A. [Center for Direct Catalytic Conversion Of Biomass to Biofuels (C3Bio), Purdue University, West Lafayette IN USA; Department of Horticulture, Purdue University, West Lafayette IN USA; Department of Plant Science and Landscape Architecture, University of Maryland, College Park MD USA; Department of Environmental Science and Technology, University of Maryland, College Park MD USA

    2016-04-07

    Conversion of nongrain biomass into liquid fuel is a sustainable approach to energy demands as global population increases. Previously, we showed that iron can act as a catalyst to enhance the degradation of lignocellulosic biomass for biofuel production. However, direct addition of iron catalysts to biomass pretreatment is diffusion-limited, would increase the cost and complexity of biorefinery unit operations and may have deleterious environmental impacts. Here, we show a new strategy for in planta accumulation of iron throughout the volume of the cell wall where iron acts as a catalyst in the deconstruction of lignocellulosic biomass. We engineered CBM-IBP fusion polypeptides composed of a carbohydrate-binding module family 11 (CBM11) and an iron-binding peptide (IBP) for secretion into Arabidopsis and rice cell walls. CBM-IBP transformed Arabidopsis and rice plants show significant increases in iron accumulation and biomass conversion compared to respective controls. Further, CBM-IBP rice shows a 35% increase in seed iron concentration and a 40% increase in seed yield in greenhouse experiments. CBM-IBP rice potentially could be used to address iron deficiency, the most common and widespread nutritional disorder according to the World Health Organization.

  12. Na(+)/H(+) Exchanger 9 Regulates Iron Mobilization at the Blood-Brain Barrier in Response to Iron Starvation.

    Science.gov (United States)

    Beydoun, Rami; Hamood, Mohamed A; Gomez Zubieta, Daniela M; Kondapalli, Kalyan C

    2017-03-10

    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. In hBMVECs, we show that NHE9 expression is up-regulated very early in a physiological response invoked by paracrine signals from iron-starved astrocytes. Ectopic expression of NHE9 in hBMVECs without external cues induced up-regulation of the transferrin receptor (TfR) and down-regulation of ferritin, leading to an increase in iron uptake. Mechanistically, we demonstrate that NHE9 localizes to recycling endosomes in hBMVECs where it raises the endosomal pH. The ensuing alkalization of the endosomal lumen increased translocation of TfRs to the hBMVEC membrane. TfRs on the membrane were previously shown to facilitate both recycling-dependent and -independent iron uptake. We propose that NHE9 regulates TfR-dependent, recycling-independent iron uptake in hBMVECs by fine-tuning the endosomal pH in response to paracrine signals and is therefore an important regulator in iron mobilization pathway at the BBB. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  13. Specific expression of the vacuolar iron transporter, TgVit, causes iron accumulation in blue-colored inner bottom segments of various tulip petals.

    Science.gov (United States)

    Momonoi, Kazumi; Tsuji, Toshiaki; Kazuma, Kohei; Yoshida, Kumi

    2012-01-01

    Several flowers of Tulipa gesneriana exhibit a blue color in the bottom segments of the inner perianth. We have previously reported the inner-bottom tissue-specific iron accumulation and expression of the vacuolar iron transporter, TgVit1, in tulip cv. Murasakizuisho. To clarify whether the TgVit1-dependent iron accumulation and blue-color development in tulip petals are universal, we analyzed anthocyanin, its co-pigment components, iron contents and the expression of TgVit1 mRNA in 13 cultivars which show a blue color in the bottom segments of the inner perianth accompanying yellow- and white-colored inner-bottom petals. All of the blue bottom segments contained the same anthocyanin component, delphinidin 3-rutinoside. The flavonol composition varied with cultivar and tissue part. The major flavonol in the bottom segments of the inner perianth was rutin. The iron content in the upper part was less than that in the bottom segments of the inner perianth. The iron content in the yellow and white petals was higher in the bottom segment of the inner perianth than in the upper tissues. TgVit1 mRNA expression was apparent in all of the bottom tissues of the inner perianth. The result of a reproduction experiment by mixing the constituents suggests that the blue coloration in tulip petals is generally caused by iron complexation to delphinidin 3-rutinoside and that the iron complex is solubilized and stabilized by flavonol glycosides. TgVit1-dependent iron accumulation in the bottom segments of the inner perianth might be controlled by an unknown system that differentiated the upper parts and bottom segments of the inner perianth.

  14. Interaction between cadmium and iron. Accumulation and distribution of metals and changes in growth parameters of Phaseolus vulgaris L. seedlings

    Directory of Open Access Journals (Sweden)

    Anna Siedlecka

    2014-01-01

    Full Text Available The interaction between cadmium, one of the most toxic heavy metals, and iron, an essential plant nutritional element, was investigated in Phaseolus vulgaris L. (cv. Słowianka seedlings. The interaction was externally induced by changing the content of both metals in the nutrient medium. Under iron deficiency conditions (0 and 0.5 of normal dose of this element, the toxic effects of cadmium on plant growth parameters, like fresh and dry weight accumulation, primary leaves area, etc., were generally much more pronounced than under normal iron supply. At normal and excess iron supply (1, 2 and 4 doses cadmium diminished iron accumulation in roots and primary leaves, but on the other hand excess iron decreased cadmium level, preventing plants from extreme toxicity of very high cadmium concentrations in the growth environment. It is to be noted that iron is classified also as a heavy metal, and its excess may become toxic, e.g. decreasing root dry weight or diminishing leaf area, especially at the highest dose. The detoxication role of iron against cadmium, and possibly other toxic metals is, however, limited to concentrations of this element in the nutrient solution which themselves are not toxic for the organism.

  15. Zinc and selenium accumulation and their effect on iron bioavailability in common bean seeds.

    Science.gov (United States)

    de Figueiredo, Marislaine A; Boldrin, Paulo F; Hart, Jonathan J; de Andrade, Messias J B; Guilherme, Luiz R G; Glahn, Raymond P; Li, Li

    2017-02-01

    Common beans (Phaseolus vulgaris) are the most important legume crops. They represent a major source of micronutrients and a target for essential trace mineral enhancement (i.e. biofortification). To investigate mineral accumulation during seed maturation and to examine whether it is possible to biofortify seeds with multi-micronutrients without affecting mineral bioavailability, three common bean cultivars were treated independently with zinc (Zn) and selenium (Se), the two critical micronutrients that can be effectively enhanced via fertilization. The seed mineral concentrations during seed maturation and the seed Fe bioavailability were analyzed. Common bean seeds were found to respond positively to Zn and Se treatments in accumulating these micronutrients. While the seed pods showed a decrease in Zn and Se along with Fe content during pod development, the seeds maintained relatively constant mineral concentrations during seed maturation. Selenium treatment had minimal effect on the seed accumulation of phytic acid and polyphenols, the compounds affecting Fe bioavailability. Zinc treatment reduced phytic acid level, but did not dramatically affect the concentrations of total polyphenols. Iron bioavailability was found not to be greatly affected in seeds biofortified with Se and Zn. In contrast, the inhibitory polyphenol compounds in the black bean profoundly reduced Fe bioavailability. These results provide valuable information for Se and Zn enhancement in common bean seeds and suggest the possibility to biofortify with these essential nutrients without greatly affecting mineral bioavailability to increase the food quality of common bean seeds. Published by Elsevier Masson SAS.

  16. Altered expression of iron regulatory proteins with aging is associated with transient hepatic iron accumulation after environmental heat stress.

    Science.gov (United States)

    Bloomer, Steven A; Han, Okhee; Kregel, Kevin C; Brown, Kyle E

    2014-01-01

    An increasing body of evidence suggests that dysregulation of iron metabolism contributes to age-related pathologies. We have previously observed increased hepatic iron with aging, and that environmental heat stress stimulates a further increase in iron and oxidative liver injury in old rats. The purpose of this study was to determine a mechanism for the increase in hepatic iron in old rats after heat stress. Young (6 mo) and old (24 mo) Fischer 344 rats were exposed to two heating bouts separated by 24 h. Livers were harvested after the second heat stress, and protein levels of the iron import protein, transferrin receptor-1 (TFR1), and the iron export protein, ferroportin (Fpn) were determined by immunoblot. In the nonheated condition, old rats had lower TFR1 expression, and higher Fpn expression. After heat stress, TFR1 declined in the old rats, and iron chelation studies demonstrated that this decline was dependent on a hyperthermia-induced increase in iron. TFR1 did not change in the young rats after heat stress. Since TFR1 is inversely regulated by iron, our results suggest that the increase in intracellular iron with aging and heat stress lower TFR1 expression. Fpn expression increased in both age groups after heat stress, but this response was delayed in old rats. This delay in the induction of an iron exporter suggests a mechanism for the increase in hepatic iron and oxidative injury after heat stress in aged organisms. © 2013.

  17. Are Lotus species good models for studying iron accumulation in common beans?

    DEFF Research Database (Denmark)

    Orlowska, Elzbieta; Laszcyca, Katarzyna Malgorzata; Urbanski, Dorian Fabian

    , and the effects of different concentrations of iron in the growth media on the plants' iron concentration. Our studies indicate that Lotus plants are good model organisms for studying seed iron loading in legumes. The work was supported by HarvestPlus, 2033 K Street, NW, Washington DC 20006-1002, USA......  Iron is an important micronutrient for all living organisms. Although iron is abundant in the Earth's crust, iron deficiency is a common problem throughout the food chain. Legume seeds have relatively high but also highly variable iron content. Little is known about the mechanisms controlling...... seed iron loading and only a few genes involved in seed iron metabolism have been described. Understanding the mechanisms that control seed iron loading and iron bioavailability can assist in breeding legumes with more bioavailable iron.             The aim of our study is to find Lotus genes...

  18. [Effects of exogenous iron on lead accumulation in Typha latifolia from a lead-contaminated soil].

    Science.gov (United States)

    Zhong, Shun-Qing; Xu, Jian-Ming

    2013-01-01

    A pot experiment was conducted to study the effects of adding 100 and 500 mg x kg(-1) of exogenous iron (Fe) on the lead (Pb) accumulation in Typha latifolia growing on a soil with 0, 100, 500 and 1000 mg x kg(-1) of Pb, respectively. In treatment 500 mg Fe x kg(-1), the Pb concen tration in T. latifolia shoots and roots was higher, compared with that in treatment 100 mg Fe x kg(-1). When the soil Pb concentration was 1000 mg x kg(-1), the Pb concentration in T. lati folia shoots and roots in treatment 500 mg Fe x kg(-1) increased by 33.7% and 50.5%, respectively, compared with that in treatment 100 mg Fe x kg(-1). The exchangeable Pb concentration in rhizosphere soil was 77.0% -114.6% higher in treatment 500 mg Fe x kg(-1) than in treatment 100 mg Fe x kg(-1). When the soil Pb concentration was 0, 100 and 1000 mg x kg(-1), the root dry mass in treatment 500 mg Fe x kg(-1) had a significant decrease, compared with that in treatment 100 mg Fe x kg(-1). It was suggested that adding appropriate amount of Fe to Pb-contaminated wetland soil could increase the availability of soil Pb and improve the Pb accumulation in plants.

  19. No evidence for substrate accumulation in Parkinson brains with GBA mutations.

    Science.gov (United States)

    Gegg, Matthew E; Sweet, Lindsay; Wang, Bing H; Shihabuddin, Lamya S; Sardi, Sergio Pablo; Schapira, Anthony H V

    2015-07-01

    To establish whether Parkinson's disease (PD) brains previously described to have decreased glucocerebrosidase activity exhibit accumulation of the lysosomal enzyme's substrate, glucosylceramide, or other changes in lipid composition. Lipidomic analyses and cholesterol measurements were performed on the putamen (n = 5-7) and cerebellum (n = 7-14) of controls, Parkinson's disease brains with heterozygote GBA1 mutations (PD+GBA), or sporadic PD. Total glucosylceramide levels were unchanged in both PD+GBA and sporadic PD brains when compared with controls. No changes in glucosylsphingosine (deacetylated glucosylceramide), sphingomyelin, gangliosides (GM2, GM3), or total cholesterol were observed in either putamen or cerebellum. This study did not demonstrate glucocerebrosidase substrate accumulation in PD brains with heterozygote GBA1 mutations in areas of the brain with low α-synuclein pathology. © 2015 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

  20. Kinetics of Transferrin and Transferrin-Receptor during Iron Transport through Blood Brain Barrier

    Science.gov (United States)

    Khan, Aminul; Liu, Jin; Dutta, Prashanta

    2017-11-01

    Transferrin and its receptors play an important role during the uptake and transcytosis of iron by blood brain barrier (BBB) endothelial cells to maintain iron homeostasis in BBB endothelium and brain. In the blood side of BBB, ferric iron binds with the apo-transferrin to form holo-transferrin which enters the endothelial cell via transferrin receptor mediated endocytosis. Depending on the initial concentration of iron inside the cell endocytosed holo-transferrin can either be acidified in the endosome or exocytosed through the basolateral membrane. Acidification of holo-transferrin in the endosome releases ferrous irons which may either be stored and used by the cell or transported into brain side. Exocytosis of the holo-transferrin through basolateral membrane leads to transport of iron bound to transferrin into brain side. In this work, kinetics of internalization, recycling and exocytosis of transferrin and its receptors are modeled by laws of mass action during iron transport in BBB endothelial cell. Kinetic parameters for the model are determined by least square analysis. Our results suggest that the cell's initial iron content determines the extent of the two possible iron transport pathways, which will be presented in this talk Research reported in this publication was supported by the National Institute of General Medical Sciences of the National Institutes of Health under Award Number R01GM122081.

  1. Oxidative stress and damage in liver, but not in brain, of Fischer 344 rats subjected to dietary iron supplementation with lipid-soluble[(3,5,5-Trimethylhexanoyl)ferrocene

    DEFF Research Database (Denmark)

    Lykkesfeldt, Jens; Morgan, Evan; Christen, Stephan

    2007-01-01

    Accumulation of iron probably predisposes the aging brain to progressive neuronal loss. We examined various markers of oxidative stress and damage in the brain and liver of 3- and 24-month old rats following supplementationwith the lipophilic iron derivative [(3,5,5-trimethylhexanoyl......TMHF. In contrast,TMHFtreatment increased the level of HO-1 in Kupffer cells, NT in hepatic endothelial cells, and MDA and ferritin in hepatocytes. Although these results demonstrated an increase in the biochemical markers of oxidative stress and damage in response to increasing concentrations of iron in the liver......)ferrocene] (TMHF), which is capable of crossing the blood-brain barrier. At both ages, iron concentration increased markedly in the liver but failed to increase in the brain. In the liver of TMHF-treated young rats, levels of a- and ¿-tocopherols and glutathione (GSH) were also higher. In contrast, the brain...

  2. Accumulation of pantothenic acid by the isolated choroid plexus and brain slices in vitro. [Rabbits

    Energy Technology Data Exchange (ETDEWEB)

    Spector, R.; Boose, B.

    1984-08-01

    In vitro, the transport of (/sup 14/C)pantothenic acid into and from the isolated rabbit choroid plexus, an anatomical locus of the blood-CSF barrier, and brain slices was studied. The choroid plexus accumulated (/sup 14/C)pantothenic acid from the medium against a concentration gradient, although at low concentrations (less than 1 microM) there was substantial intracellular phosphorylation and binding of the (/sup 14/C)pantothenic acid. The saturable accumulation process in choroid plexus was inhibited by probenecid and caproic acid but not by nicotinic acid or by weak bases. The accumulation process was markedly inhibited by N-ethylmaleimide, poly-L-lysine (which blocks sodium transport), and low temperatures. (/sup 14/C)Pantothenic acid was readily released from choroid plexus by a temperature-dependent process. Brain slices also accumulated and, at low concentrations, phosphorylated (/sup 14/C)pantothenic acid from the medium by a temperature-, probenecid-, and N-ethylmaleimide-sensitive saturable process. However, unlike choroid plexus, brain slices did not concentrate free pantothenic acid and (/sup 14/C)pantothenic acid accumulation was not sensitive to poly-L-lysine. (/sup 14/C)Pantothenic acid was readily released from brain slices by a temperature-sensitive process. These results are consistent with the view that (/sup 14/C)pantothenic acid enters the isolated choroid plexus and brain slices by active transport and facilitated diffusion, respectively.

  3. Impairment of interrelated iron- and copper homeostatic mechanisms in brain contributes to the pathogenesis of neurodegenerative disorders

    DEFF Research Database (Denmark)

    Skjørringe, Tina; Møller, Lisbeth Birk; Moos, Torben

    2012-01-01

    Iron and copper are important co-factors for a number of enzymes in the brain, including enzymes involved in neurotransmitter synthesis and myelin formation. Both shortage and an excess of iron or copper will affect the brain. The transport of iron and copper into the brain from the circulation...... is strictly regulated, and concordantly protective barriers, i.e., the blood-brain barrier (BBB) and the blood-cerebrospinal fluid (CSF) barrier (BCB) have evolved to separate the brain environment from the circulation. The uptake mechanisms of the two metals interact. Both iron deficiency and overload lead......) is involved in the uptake of both iron and copper. Furthermore, copper is an essential co-factor in numerous proteins that are vital for iron homeostasis and affects the binding of iron-response proteins to iron-response elements in the mRNA of the transferrin receptor, DMT1, and ferroportin, all highly...

  4. Iron Oxide Nanoparticle Delivery of Peptides to the Brain: Reversal of Anxiety during Drug Withdrawal

    OpenAIRE

    Nathan Vinzant; Scholl, Jamie L.; Chia-Ming Wu; Trevor Kindle; Ranjit Koodali; Gina L. Forster

    2017-01-01

    Targeting neuropeptide systems is important for future advancements in treatment of neurological and psychiatric illnesses. However, many of the peptides and their analogs do not cross the blood-brain barrier (BBB) efficiently. Nanoparticles such as iron oxide can cross the BBB, and here we describe a novel method for the conjugation of a peptide antisauvagine-30 (ASV-30) to iron oxide nanoparticles. Previous research has shown that direct infusion of ASV-30 into the brain reduces anxiety-lik...

  5. Dopamine promotes cellular iron accumulation and oxidative stress responses in macrophages.

    Science.gov (United States)

    Dichtl, Stefanie; Haschka, David; Nairz, Manfred; Seifert, Markus; Volani, Chiara; Lutz, Oliver; Weiss, Günter

    2017-12-02

    Iron is essential for many biological functions including neurotransmitter synthesis, where the metal is a co-factor of tyrosine hydroxylase, which converts tyrosine to dopamine and further to norepinephrine. As the shared chemical structure, called catechol, may potentially bind iron we questioned whether tyrosine derived hormones would impact on cellular iron homeostasis in macrophages, which are central for the maintenance of body iron homeostasis. Using murine bone marrow-derived macrophages (BMDMs), we investigated the effect of catecholamines and found that only dopamine but neither tyrosine, nor norepinephrine, affected cellular iron homeostasis. Exposure of macrophages to dopamine increased the uptake of non-transferrin bound iron into cells. The expansion of intracellular iron upon dopamine treatment resulted in oxidative stress responses as evidenced by increased expression of nuclear factor erythroid 2-related factor (Nrf2) and hypoxia inducible factor-1α. As a consequence, the transcriptional expression of stress response genes such as heme oxygenase-1 and the iron export protein ferroportin1 were significantly increased. Genetic deletion of Nrf2 abolished these effects of dopamine. Dopamine directly affects cellular iron homeostasis by increasing iron incorporation into macrophages and subsequently promoting intracellular oxidative stress responses. Our observations are of interest for disorders involving dopamine and iron dyshomeostasis such as Parkinson's disease and restless legs syndrome, partly enlightening the underlying pathology or the therapeutic efficacy of dopamine agonists to overcome neuronal iron deficiency. Copyright © 2017. Published by Elsevier Inc.

  6. The Acute Effect of Humic Acid on Iron Accumulation in Rats.

    Science.gov (United States)

    Cagin, Yasir Furkan; Sahin, N; Polat, A; Erdogan, M A; Atayan, Y; Eyol, E; Bilgic, Y; Seckin, Y; Colak, C

    2016-05-01

    Free iron leads to the formation of pro-oxidant reactive oxygen species (ROS). Humic acids (HAs) enhance permeability of cellular wall and act as a chelator through electron transferring. This study was designed to test chelator effect of HA on iron as well as its anti-oxidant effect against the iron-induced hepatotoxicity and cardiotoxicity. The rats used were randomly divided into four groups (n = 8/group): group I (the control group); group II (the HA group), humic acid (562 mg/kg) was given over 10 days by oral gavage; group III (the iron group), iron III hydroxide polymaltose (250 mg/kg) was given over 10 days by intraperitoneal route; and group IV (the HA plus iron group), received the iron (similar to group II) plus humic acid (similar to those in groups II and III) group. Blood and two tissue samples both from liver and heart were obtained for biochemical and histopathological evaluations. Iron deposition, the iron-induced hepatotoxicity, and cardiotoxicity were demonstrated by histopathological and biochemical manner. However, no significant differences were observed in the serum biochemical values and the histopathological results among the iron and the HA plus iron groups in the liver tissue but not in the heart tissue. The protective effects of humic acid against iron-induced cardiotoxicity were shown but not against hepatotoxicity in our study.

  7. Branched-chain amino acids reduce hepatic iron accumulation and oxidative stress in hepatitis C virus polyprotein-expressing mice

    Science.gov (United States)

    Korenaga, Masaaki; Nishina, Sohji; Korenaga, Keiko; Tomiyama, Yasuyuki; Yoshioka, Naoko; Hara, Yuichi; Sasaki, Yusuke; Shimonaka, Yasushi; Hino, Keisuke

    2015-01-01

    Background & Aims Branched-chain amino acids (BCAA) reduce the incidence of hepatocellular carcinoma (HCC) in patients with cirrhosis. However, the mechanisms that underlie these effects remain unknown. Previously, we reported that oxidative stress in male transgenic mice that expressed hepatitis C virus polyprotein (HCVTgM) caused hepatic iron accumulation by reducing hepcidin transcription, thereby leading to HCC development. This study investigated whether long-term treatment with BCAA reduced hepatic iron accumulation and oxidative stress in iron-overloaded HCVTgM and in patients with HCV-related advanced fibrosis. Methods Male HCVTgM were fed an excess-iron diet that comprised either casein or 3.0% BCAA, or a control diet, for 6 months. Results For HCVTgM, BCAA supplementation increased the serum hepcidin-25 levels and antioxidant status [ratio of biological antioxidant potential (BAP) relative to derivatives of reactive oxygen metabolites (dROM)], decreased the hepatic iron contents, attenuated reactive oxygen species generation, and restored mitochondrial superoxide dismutase expression and mitochondrial complex I activity in the liver compared with mice fed the control diet. After 48 weeks of BCAA supplementation in patients with HCV-related advanced fibrosis, BAP/dROM and serum hepcidin-25 increased and serum ferritin decreased compared with the pretreatment levels. Conclusions BCAA supplementation reduced oxidative stress by restoring mitochondrial function and improved iron metabolism by increasing hepcidin-25 in both iron-overloaded HCVTgM and patients with HCV-related advanced fibrosis. These activities of BCAA may partially account for their inhibitory effects on HCC development in cirrhosis patients. PMID:25156780

  8. Age dependent accumulation of N-acyl-ethanolamine phospholipids in ischemic rat brain

    DEFF Research Database (Denmark)

    Moesgaard, B.; Petersen, G.; Hansen, Harald S.

    2000-01-01

    N-acyl-ethanolamine phospholipids (NAPE) can be formed as a stress response during neuronal injury, and they are precursors for N-acyl- ethanolamines (NAE), some of which are endocannabinoids. The levels of NAPE accumulated during post-decapitative ischemia (6 h at 37°C) were studied in rat brains...... of various age (1, 6, 12, 19, 30, and ~70 days) by the use of P NMR spectroscopy of lipid extracts. This ability to accumulate NAPE was compared with the activity of N-acyltransferase and of NAPE-hydrolyzing phospholipase D (NAPE-PLD) in brain microsomes. These two enzymes are involved in the formation...... and degradation of NAPE, respectively. The results showed that 1) the ability to accumulate NAPE during post-decapitative ischemia is especially high in the youngest rats and is markedly reduced in older brains [in 1-day-old rat brains NAPE accumulated to 1.5% of total phospholipids, while in 30-day-old rat...

  9. Low density lipoprotein inhibits accumulation of nitrites in murine brain endothelial cell cultures.

    Science.gov (United States)

    Bereta, M; Bereta, J; Cohen, S; Cohen, M C

    1992-07-15

    Endothelial cells produce nitric oxide which is considered to serve as a major source of endothelial derived relaxing factor activity. It has been demonstrated that activation of mouse brain endothelium by TNF-alpha and IFN-gamma led to accumulation of nitrite which is presumably formed by oxidation of nitric oxide. A number of studies suggest that reactive oxygen species produced by cytokine-activated cells are involved in the conversion of nitric oxide to nitrites and nitrates. We investigated whether low density lipoprotein (LDL), acting as a radical scavenger, is able to inhibit nitrite accumulation in mouse brain endothelial cell cultures and in a cell-free system in which sodium nitroprusside was used as a source of nitric oxide. A comparison of these two models indicates the active involvement of LDL in suppressing nitrite accumulation in murine endothelial cultures.

  10. Quantitative estimation of regional brain iron with magnetic resonance imaging.

    Science.gov (United States)

    Martin, W R Wayne

    2009-12-01

    Biochemical studies have reported increased iron content in the substantia nigra pars compacta (SNc) in Parkinson disease (PD), with changes most marked in severe disease, suggesting that measurement of regional iron content in the nigra may provide an indication of the pathologic severity of the disease. Although basal ganglia structures, including the substantia nigra, are readily visualized with MRI, in part because of their high iron content, conventional imaging techniques have failed to show definitive abnormalities in individuals with PD. We have developed MRI-based methodology to estimate regional iron content utilizing a 1.5 tesla system and have shown a correlation between age and striatal iron, as well as a significant increase in putaminal and pallidal iron in PD that correlated with the severity of clinical symptomatology. Several investigators have utilized novel MR techniques implemented on 3 tesla magnets and have suggested the presence of increased nigral iron content in treated patients with PD, in addition to a correlation between nigral iron and simple reaction time. We have applied a modification of our original method to determine whether SNc changes evident at 3 tesla corresponded anatomically to the distribution of neuropathologic changes reported previously. Our results indicate the presence of lateral SNc abnormalities in untreated patients with early PD, consistent with increased iron content and corresponding to the known distribution of neuronal loss occurring in this disorder. We suggest that this may ultimately provide an imaging marker for disease progression in PD, although longitudinal studies are required.

  11. Multiple blood-brain barrier transport mechanisms limit bumetanide accumulation, and therapeutic potential, in the mammalian brain.

    Science.gov (United States)

    Römermann, Kerstin; Fedrowitz, Maren; Hampel, Philip; Kaczmarek, Edith; Töllner, Kathrin; Erker, Thomas; Sweet, Douglas H; Löscher, Wolfgang

    2017-05-01

    There is accumulating evidence that bumetanide, which has been used over decades as a potent loop diuretic, also exerts effects on brain disorders, including autism, neonatal seizures, and epilepsy, which are not related to its effects on the kidney but rather mediated by inhibition of the neuronal Na-K-Cl cotransporter isoform NKCC1. However, following systemic administration, brain levels of bumetanide are typically below those needed to inhibit NKCC1, which critically limits its clinical use for treating brain disorders. Recently, active efflux transport at the blood-brain barrier (BBB) has been suggested as a process involved in the low brain:plasma ratio of bumetanide, but it is presently not clear which transporters are involved. Understanding the processes explaining the poor brain penetration of bumetanide is needed for developing strategies to improve the brain delivery of this drug. In the present study, we administered probenecid and more selective inhibitors of active transport carriers at the BBB directly into the brain of mice to minimize the contribution of peripheral effects on the brain penetration of bumetanide. Furthermore, in vitro experiments with mouse organic anion transporter 3 (Oat3)-overexpressing Chinese hamster ovary cells were performed to study the interaction of bumetanide, bumetanide derivatives, and several known inhibitors of Oats on Oat3-mediated transport. The in vivo experiments demonstrated that the uptake and efflux of bumetanide at the BBB is much more complex than previously thought. It seems that both restricted passive diffusion and active efflux transport, mediated by Oat3 but also organic anion-transporting polypeptide (Oatp) Oatp1a4 and multidrug resistance protein 4 explain the extremely low brain concentrations that are achieved after systemic administration of bumetanide, limiting the use of this drug for targeting abnormal expression of neuronal NKCC1 in brain diseases. Copyright © 2017 Elsevier Ltd. All rights

  12. Iron accumulation, glutathione depletion, and lipid peroxidation must occur simultaneously during ferroptosis and are mutually amplifying events.

    Science.gov (United States)

    Bertrand, Robert L

    2017-04-01

    Ferroptosis is a recently discovered form of regulated necrosis that involves iron-dependent lipid peroxidation. How cells die once ferroptosis is triggered remains unclear. Ferroptosis is hypothesized to require three critical events: (1) accumulation of redox-active iron, (2) glutathione depletion, and (3) lipid peroxidation. It is proposed that these three events must unfold simultaneously because stopping any critical event also stops ferroptosis. These events are hypothesized to amplify in severity through positive feedback loops. The cause of death in ferroptosis is therefore the synergistic combination of antioxidant depletion, iron toxicity, and membrane denaturation. The relevance of these feedback loops for cancer and neurodegenerative therapies is discussed. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Fluid-Attenuated Inversion Recovery Hypointensity of the Pulvinar Nucleus of Patients with Alzheimer Disease: Its Possible Association with Iron Accumulation as Evidenced by the T2 Map

    Energy Technology Data Exchange (ETDEWEB)

    Moon, Won Jin; Roh, Hong Gee; Choi, Jin Woo [Dept. of Radiology, Konkuk University Medical Center, Konkuk University School of Medicine, Seoul (Korea, Republic of); Kim, Hee Jin [Dept. of Neurology, Hanyang University Medical Center, Hanyang University School of Medicine, Seoul (Korea, Republic of); Han, Seol Heui [Center for Geriatric Neuroscience Research, Konkuk University School of Medicine, Seoul (Korea, Republic of)

    2012-11-15

    We hypothesized that prominent pulvinar hypointensity in brain MRI represents the disease process due to iron accumulation in Alzheimer disease (AD). We aimed to determine whether or not the pulvinar signal intensity (SI) on the fluid-attenuated inversion recovery (FLAIR) sequences at 3.0T MRI differs between AD patients and normal subjects, and also whether the pulvinar SI is correlated with the T2 map, an imaging marker for tissue iron, and a cognitive scale. Twenty one consecutive patients with AD and 21 age-matched control subjects were prospectively included in this study. The pulvinar SI was assessed on the FLAIR image. We measured the relative SI ratio of the pulvinar to the corpus callosum. The T2 values were calculated from the T2 relaxometry map. The differences between the two groups were analyzed, by using a Student t test. The correlation between the measurements was assessed by the Pearson's correlation test. As compared to the normal white matter, the FLAIR signal intensity of the pulvinar nucleus was significantly more hypointense in the AD patients than in the control subjects (p < 0.01). The pulvinar T2 was shorter in the AD patients than in the control subjects (51.5 {+-} 4.95 ms vs. 56.5 {+-} 5.49 ms, respectively, p = 0.003). The pulvinar SI ratio was strongly correlated with the pulvinar T2 (r = 0.745, p < 0.001). When controlling for age, only the pulvinar-to-CC SI ratio was positively correlated with that of the Mini-Mental State Examination (MMSE) score (r = 0.303, p < 0.050). Conversely, the pulvinar T2 was not correlated with the MMSE score (r = 0.277, p = 0.080). The FLAIR hypointensity of the pulvinar nucleus represents an abnormal iron accumulation in AD and may be used as an adjunctive finding for evaluating AD.

  14. Assessment of heavy metal accumulation in macrophyte, agricultural soil, and crop plants adjacent to discharge zone of sponge iron factory

    Science.gov (United States)

    Gupta, S.; Nayek, S.; Saha, R. N.; Satpati, S.

    2008-08-01

    The present study deals with the characterization of effluent released from sponge iron industries and distribution of heavy metals in soil and macrophytes near to effluent discharge channel. Apart from this, accumulation of heavy metals in nearby soil and vegetation system irrigated with effluent-contaminated water is also the subject of this study. Physico-chemical analysis of effluent reveals that the concentration of total suspended solids (TSS), total hardness (TH), iron (Fe2+), and oil and grease are greater than the IS (1981) norms for discharge of water into inland water body. The soil along the sides of the effluent channel also shows higher concentration of heavy metals than the background soil. The enrichment of the heavy metals are in the order of Chromium (Cr) > Iron (Fe) > Manganese (Mn) > Zinc (Zn) > Copper (Cu) > Cadmium (Cd). Macrophytes growing along the sides of the effluent channel also show significant accumulation of heavy metals almost in the same order as accumulated in soil. Higher uptake of heavy metals by these varieties reveals that these species can be used for future phytoremediation. The effluent as well as contaminated water is extensively used for irrigation for growing vegetables like tomato ( Lycopersicon esculatum) in the surrounding areas. Heavy metal accumulation in this agricultural soil are in the sequence of Cr > Fe > Mn > Zn > Cu > Cd. More or less similar type of accumulation pattern are also found in tomato plants except Fe and Zn exceeding Cr and Mn. Transfer Factor of heavy metals from soil to tomato plants (TFS) shows average value of toxicity test will be necessary in order to identify the most resistive variety on this particular type of contaminated site.

  15. Neuroprotection of brain-permeable iron chelator VK-28 against intracerebral hemorrhage in mice.

    Science.gov (United States)

    Li, Qian; Wan, Jieru; Lan, Xi; Han, Xiaoning; Wang, Zhongyu; Wang, Jian

    2017-09-01

    Iron overload plays a key role in the secondary brain damage that develops after intracerebral hemorrhage (ICH). The significant increase in iron deposition is associated with the generation of reactive oxygen species (ROS), which leads to oxidative brain damage. In this study, we examined the protective effects of VK-28, a brain-permeable iron chelator, against hemoglobin toxicity in an ex vivo organotypic hippocampal slice culture (OHSC) model and in middle-aged mice subjected to an in vivo, collagenase-induced ICH model. We found that the effects of VK-28 were similar to those of deferoxamine (DFX), a well-studied iron chelator. Both decreased cell death and ROS production in OHSCs and in vivo, decreased iron-deposition and microglial activation around hematoma in vivo, and improved neurologic function. Moreover, compared with DFX, VK-28 polarized microglia to an M2-like phenotype, reduced brain water content, deceased white matter injury, improved neurobehavioral performance, and reduced overall death rate after ICH. The protection of VK-28 was confirmed in a blood-injection ICH model and in aged-male and young female mice. Our findings indicate that VK-28 is protective against iron toxicity after ICH and that, at the dosage tested, it has better efficacy and less toxicity than DFX does.

  16. Directed plant cell-wall accumulation of iron: embedding co-catalyst for efficient biomass conversion

    Science.gov (United States)

    Chien-Yuan Lin; Joseph E. Jakes; Bryon S. Donohoe; Peter N. Ciesielski; Haibing Yang; Sophie-Charlotte Gleber; Stefan Vogt; Shi-You Ding; Wendy A. Peer; Angus S. Murphy; Maureen C. McCann; Michael E. Himmel; Melvin P. Tucker; Hui Wei

    2016-01-01

    Background: Plant lignocellulosic biomass is an abundant, renewable feedstock for the production of biobased fuels and chemicals. Previously, we showed that iron can act as a co-catalyst to improve the deconstruction of lignocellulosic biomass. However, directly adding iron catalysts into biomass prior to pretreatment is diffusion limited,...

  17. The brains of bats foraging at wastewater treatment works accumulate arsenic, and have low non-enzymatic antioxidant capacities.

    Science.gov (United States)

    Hill, Kate; Schoeman, M Corrie; Vosloo, Dalene

    2017-12-14

    Increasing rates of urbanisation cause ubiquitous infrastructures that remove anthropogenic contaminants - particularly Wastewater Treatment Works (WWTWs) - to become stressed, and hence pollute surrounding water systems. Neoromicia nana bats are suitable models to study the effects of pollution in these environments because they exploit abundant pollutant-tolerant chironomid midges that breed at WWTWs, and consequently accumulate metals such as iron, copper and zinc in their livers and kidneys. If these metals persist in their circulatory systems, and cross the blood brain barrier (BBB) they can have adverse effects on critical functions such as flight and echolocation. The aim of this study was to investigate the potential neurological effects on N. nana foraging at WWTWs versus bats at reference sites in Durban, South Africa. Our objectives were to 1) compare trace metal levels in brain and hair samples (as a proxy for circulating metals) between N. nana foraging at WWTWs and reference sites to determine if excess metals pass through the BBB via the circulatory system; and 2) compare biomarkers of neuron function (acetylcholinesterase activity), protection (antioxidant capacity), DNA integrity (DNA fragmentation), lipid integrity (lipid peroxidation) and cell viability (caspase-3 activity) between N. nana foraging at WWTW and reference sites. We found a significantly higher concentration of arsenic in hair (p < 0.05) and brain tissue (p < 0.1) of WWTW bats compared to bats at reference sites. By contrast, acetylcholinesterase activity did not differ in bats among sites and there was no evidence of significant differences in lipid peroxidation, compromised DNA integrity or apoptosis in the brains between WWTW bats and reference site bats. However, total antioxidant capacity was significantly lower in brains of WWTW bats than bats at reference sites suggesting that antioxidant protection may be compromised. Long-term exposure to environmental pollutants at

  18. Iron Oxide Nanoparticle Delivery of Peptides to the Brain: Reversal of Anxiety during Drug Withdrawal

    Science.gov (United States)

    Vinzant, Nathan; Scholl, Jamie L.; Wu, Chia-Ming; Kindle, Trevor; Koodali, Ranjit; Forster, Gina L.

    2017-01-01

    Targeting neuropeptide systems is important for future advancements in treatment of neurological and psychiatric illnesses. However, many of the peptides and their analogs do not cross the blood-brain barrier (BBB) efficiently. Nanoparticles such as iron oxide can cross the BBB, and here we describe a novel method for the conjugation of a peptide antisauvagine-30 (ASV-30) to iron oxide nanoparticles. Previous research has shown that direct infusion of ASV-30 into the brain reduces anxiety-like behavior in animal models via actions on corticotropin releasing factor type 2 (CRF2) receptors. Therefore, we tested whether iron oxide+ASV-30 complexes cross the BBB of rats and then determined whether iron oxide+ASV-30 nanoparticles are localized with CRF2-expressing neurons. Finally we tested the hypothesis that systemic infusion of iron oxide+ASV-30 can reduce anxiety-like behavior. First we describe the synthesis and demonstrate the stability of iron oxide-peptide nanoparticle complexes. Next, nanoparticles (87.7 μg/kg Fe2O3) with or without ASV-30 (200 μg/kg, ip) were injected into male rats 30 min prior to transcardial perfusion and brain fixation for immunohistochemical analysis, or before testing on the elevated plus maze (EPM) in an amphetamine withdrawal model of anxiety. Systemically administered iron oxide+ASV-30 particles were present in the brain and associated with neurons, including those that express CRF2 receptors, but did not localize with the iron storage protein ferritin. Furthermore, systemic administration of ironoxide+ASV-30 reduced amphetamine withdrawal-induced anxiety without affecting locomotion, suggesting that the anxiolytic effects of ASV-30 were preserved and the bioavailability of ASV-30 was sufficient. The findings demonstrate a novel approach to peptide delivery across the BBB and provide insight as to the neural distribution and efficacy of this nanotechnology. PMID:29163012

  19. Iron Oxide Nanoparticle Delivery of Peptides to the Brain: Reversal of Anxiety during Drug Withdrawal

    Directory of Open Access Journals (Sweden)

    Nathan Vinzant

    2017-11-01

    Full Text Available Targeting neuropeptide systems is important for future advancements in treatment of neurological and psychiatric illnesses. However, many of the peptides and their analogs do not cross the blood-brain barrier (BBB efficiently. Nanoparticles such as iron oxide can cross the BBB, and here we describe a novel method for the conjugation of a peptide antisauvagine-30 (ASV-30 to iron oxide nanoparticles. Previous research has shown that direct infusion of ASV-30 into the brain reduces anxiety-like behavior in animal models via actions on corticotropin releasing factor type 2 (CRF2 receptors. Therefore, we tested whether iron oxide+ASV-30 complexes cross the BBB of rats and then determined whether iron oxide+ASV-30 nanoparticles are localized with CRF2-expressing neurons. Finally we tested the hypothesis that systemic infusion of iron oxide+ASV-30 can reduce anxiety-like behavior. First we describe the synthesis and demonstrate the stability of iron oxide-peptide nanoparticle complexes. Next, nanoparticles (87.7 μg/kg Fe2O3 with or without ASV-30 (200 μg/kg, ip were injected into male rats 30 min prior to transcardial perfusion and brain fixation for immunohistochemical analysis, or before testing on the elevated plus maze (EPM in an amphetamine withdrawal model of anxiety. Systemically administered iron oxide+ASV-30 particles were present in the brain and associated with neurons, including those that express CRF2 receptors, but did not localize with the iron storage protein ferritin. Furthermore, systemic administration of ironoxide+ASV-30 reduced amphetamine withdrawal-induced anxiety without affecting locomotion, suggesting that the anxiolytic effects of ASV-30 were preserved and the bioavailability of ASV-30 was sufficient. The findings demonstrate a novel approach to peptide delivery across the BBB and provide insight as to the neural distribution and efficacy of this nanotechnology.

  20. Dystonia with Brain Manganese Accumulation Resulting From SLC30A10 Mutations: A New Treatable Disorder

    OpenAIRE

    Stamelou, Maria; Tuschl, Karin; Chong, W.K.; Andrew K. Burroughs; Mills, Philippa B.; Bhatia, Kailash P.; Clayton, Peter T.

    2012-01-01

    Background The first gene causing early-onset generalized dystonia with brain manganese accumulation has recently been identified. Mutations in the SLC30A10 gene, encoding a manganese transporter, cause a syndrome of hepatic cirrhosis, dystonia, polycythemia, and hypermanganesemia. Methods We present 10-year longitudinal clinical features, MRI data, and treatment response to chelation therapy of the originally described patient with a proven homozygous mutation in SLC30A10. Results The patien...

  1. Glucose-6-phosphate reduces calcium accumulation in rat brain endoplasmic reticulum

    Directory of Open Access Journals (Sweden)

    Jeffrey Thomas Cole

    2012-04-01

    Full Text Available Brain cells expend large amounts of energy sequestering calcium (Ca2+, while loss of Ca2+ compartmentalization leads to cell damage or death. Upon cell entry, glucose is converted to glucose-6-phosphate (G6P, a parent substrate to several metabolic major pathways, including glycolysis. In several tissues, G6P alters the ability of the endoplasmic reticulum to sequester Ca2+. This led to the hypothesis that G6P regulates Ca2+ accumulation by acting as an endogenous ligand for sarco-endoplasmic reticulum calcium ATPase (SERCA. Whole brain ER microsomes were pooled from adult male Sprague-Dawley rats. Using radio-isotopic assays, 45Ca2+ accumulation was quantified following incubation with increasing amounts of G6P, in the presence or absence of thapsigargin, a potent SERCA inhibitor. To qualitatively assess SERCA activity, the simultaneous release of inorganic phosphate (Pi coupled with Ca2+ accumulation was quantified. Addition of G6P significantly and decreased Ca2+ accumulation in a dose-dependent fashion (1-10 mM. The reduction in Ca2+ accumulation was not significantly different that seen with addition of thapsigargin. Addition of glucose-1-phosphate or fructose-6-phosphate, or other glucose metabolic pathway intermediates, had no effect on Ca2+ accumulation. Further, the release of Pi was markedly decreased, indicating G6P-mediated SERCA inhibition as the responsible mechanism for reduced Ca2+ uptake. Simultaneous addition of thapsigargin and G6P did decrease inorganic phosphate in comparison to either treatment alone, which suggests that the two treatments have different mechanisms of action. Therefore, G6P may be a novel, endogenous regulator of SERCA activity. Additionally, pathological conditions observed during disease states that disrupt glucose homeostasis, may be attributable to Ca2+ dystasis caused by altered G6P regulation of SERCA activity

  2. Impact of two iron(III) chelators on the iron, cadmium, lead and nickel accumulation in poplar grown under heavy metal stress in hydroponics.

    Science.gov (United States)

    Mihucz, Victor G; Csog, Árpád; Fodor, Ferenc; Tatár, Enikő; Szoboszlai, Norbert; Silaghi-Dumitrescu, Luminiţa; Záray, Gyula

    2012-04-15

    Poplar (Populus jacquemontiana var. glauca cv. Kopeczkii) was grown in hydroponics containing 10 μM Cd(II), Ni(II) or Pb(II), and Fe as Fe(III) EDTA or Fe(III) citrate in identical concentrations. The present study was designed to compare the accumulation and distribution of Fe, Cd, Ni and Pb within the different plant compartments. Generally, Fe and heavy-metal accumulation were higher by factor 2-7 and 1.6-3.3, respectively, when Fe(III) citrate was used. Iron transport towards the shoot depended on the Fe(III) chelate and, generally, on the heavy metal used. Lead was accumulated only in the root. The amounts of Fe and heavy metals accumulated by poplar were very similar to those of cucumber grown in an identical way, indicating strong Fe uptake regulation of these two Strategy I plants: a cultivar and a woody plant. The Strategy I Fe uptake mechanism (i.e. reducing Fe(III) followed by Fe(II) uptake), together with the Fe(III) chelate form in the nutrient solution had significant effects on Fe and heavy metal uptake. Poplar appears to show phytoremediation potential for Cd and Ni, as their transport towards the shoot was characterized by 51-54% and 26-48% depending on the Fe(III) supply in the nutrient solution. Copyright © 2012 Elsevier GmbH. All rights reserved.

  3. Accumulation of neurotoxic organochlorines and trace elements in brain of female European eel (Anguilla anguilla).

    Science.gov (United States)

    Bonnineau, C; Scaion, D; Lemaire, B; Belpaire, C; Thomé, J-P; Thonon, M; Leermaker, M; Gao, Y; Debier, C; Silvestre, F; Kestemont, P; Rees, J-F

    2016-07-01

    Xenobiotics such as organochlorine compounds (OCs) and metals have been suggested to play a significant role in the collapse of European eel stocks in the last decades. Several of these pollutants could affect functioning of the nervous system. Still, no information is so far available on levels of potentially neurotoxic pollutants in eel brain. In present study, carried out on female eels caught in Belgian rivers and canals, we analyzed brain levels of potentially-neurotoxic trace elements (Ag, Al, As, Cd, Co, Cr, Cu, Fe, Hg, MeHg, Mn, Ni, Pb, Sn, Sb, Zn) and OCs (Polychlorinated biphenyls, PCBs; Hexachlorocyclohexanes, HCHs; Dichlorodiphenyltrichloroethane and its metabolites, DDTs). Data were compared to levels in liver and muscle tissues. Eel brain contained very high amounts of OCs, superior to those found in the two other tissues. Interestingly, the relative abundance of PCB congeners markedly differed between tissues. In brain, a predominance of low chlorinated PCBs was noted, whereas highly chlorinated congeners prevailed in muscle and liver. HCHs were particularly abundant in brain, which contains the highest amounts of β-HCH and ϒ-HCH. p,p'-DDTs concentration was similar between brain and muscle (i.e., about twice that of liver). A higher proportion of p,p'-DDT was noticed in brain. Except for Cr and inorganic Hg, all potentially neurotoxic metals accumulated in brain to levels equal to or lower than hepatic levels. Altogether, results indicate that eel brain is an important target for organic and, to a lesser extent, for inorganic neurotoxic pollutants. Copyright © 2016 Elsevier B.V. All rights reserved.

  4. Enhanced lipid accumulation and biodiesel production by oleaginous Chlorella protothecoides under a structured heterotrophic-iron (II) induction strategy.

    Science.gov (United States)

    Li, Yuqin; Mu, Jinxiu; Chen, Di; Xu, Hua; Han, Fangxin

    2015-05-01

    A structured heterotrophic-iron (II) induction (HII) strategy was proposed to enhance lipid accumulation in oleaginous Chlorella protothecoides. C. protothecoides subjected to heterotrophic-iron (II) induction achieved a favorable lipid accumulation up to 62 % and a maximum lipid productivity of 820.17 mg/day, representing 2.78-fold and 3.64-fold increase respectively over heterotrophic cultivation alone. HII-induced cells produced significantly elevated levels of 16:0, 18:1(Δ9), and 18:2(Δ9,12) fatty acids (over 90 %). The lipid contents and plant lipid-like fatty acid compositions exhibit the potential of HII-induced C. protothecoides as biodiesel feedstock. Furthermore, 31 altered proteins in HII-induced algal cells were successfully identified. These differentially expressed proteins were assigned into nine molecular function categories, including carbohydrate metabolism, lipid biosynthesis, Calvin cycle, cellular respiration, photosynthesis, energy and transport, protein biosynthesis, regulate and defense, and unclassified. Analysis using the Kyoto encyclopedia of genes and genomes and gene ontology annotation showed that malic enzyme, acyltransferase, and ACP were key metabolic checkpoints found to modulate lipid accumulation in C. protothecoides. The results provided possible applications of HII cultivation strategy in other microalgal species and new possibilities in developing genetic and metabolic engineering microalgae for desirable lipid productivity.

  5. The effect of silicon on iron plaque formation and arsenic accumulation in rice genotypes with different radial oxygen loss (ROL).

    Science.gov (United States)

    Wu, Chuan; Zou, Qi; Xue, Sheng-Guo; Pan, Wei-Song; Huang, Liu; Hartley, William; Mo, Jing-Yu; Wong, Ming-Hung

    2016-05-01

    Rice is one of the major pathways of arsenic (As) exposure in human food chain, threatening over half of the global population. Greenhouse pot experiments were conducted to examine the effects of Si application on iron (Fe) plaque formation, As uptake and rice grain As speciation in indica and hybrid rice genotypes with different radial oxygen loss (ROL) ability. The results demonstrated that Si significantly increased root and grain biomass. Indica genotypes with higher ROL induced greater Fe plaque formation, compared to hybrid genotypes and sequestered more As in Fe plaque. Silicon applications significantly increased Fe concentrations in iron plaque of different genotypes, but it decreased As concentrations in the roots, straws and husks by 28-35%, 15-35% and 32-57% respectively. In addition, it significantly reduced DMA accumulation in rice grains but not inorganic As accumulation. Rice of indica genotypes with higher ROL accumulated lower concentrations of inorganic As in grains than hybrid genotypes with lower ROL. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. Kinetics of brain nicotine accumulation in dependent and nondependent smokers assessed with PET and cigarettes containing 11C-nicotine

    Science.gov (United States)

    Rose, Jed E.; Mukhin, Alexey G.; Lokitz, Stephen J.; Turkington, Timothy G.; Herskovic, Joseph; Behm, Frederique M.; Garg, Sudha; Garg, Pradeep K.

    2010-01-01

    Tobacco smoking is a chronic, relapsing disorder that constitutes one of the primary preventable causes of death in developed countries. Two of the popular hypotheses to explain the development and maintenance of strong nicotine dependence in cigarette smokers posit (i) a rapid brain nicotine accumulation during cigarette smoking and/or (ii) puff-associated spikes in brain nicotine concentration. To address these hypotheses, we investigated the dynamics of nicotine accumulation in the smoker's brain during actual cigarette smoking using PET with 3-s temporal resolution and 11C-nicotine loaded into cigarettes. The results of the study, performed in 13 dependent smokers (DS) and 10 nondependent smokers (NDS), suggest that puff-associated spikes in the brain nicotine concentration do not occur during habitual cigarette smoking. Despite the presence of a puff-associated oscillation in the rate of nicotine accumulation, brain nicotine concentration gradually increases during cigarette smoking. The results further suggest that DS have a slower process of brain nicotine accumulation than NDS because they have slower nicotine washout from the lungs and that DS have a tendency to compensate for their slower rate of brain nicotine accumulation compared with NDS by inhaling a larger volume of smoke. For these reasons, smokers’ dependence on cigarette smoking, or the resistance of NDS to becoming dependent, cannot be explained solely by a faster brain nicotine accumulation. PMID:20212132

  7. Measurement of helium production cross sections of iron for d-T neutrons by helium accumulation method

    Energy Technology Data Exchange (ETDEWEB)

    Takao, Yoshiyuki; Kanda, Yukinori; Nagae, Koji; Fujimoto, Toshihiro [Kyushu Univ., Fukuoka (Japan); Ikeda, Yujiro

    1997-03-01

    Helium production cross sections of Iron were measured by helium accumulation method for neutron energies from 13.5 to 14.9 MeV. Iron samples were irradiated with FNS, an intense d-T neutron source of JAERI. As the neutron energy varies according to the emission angle at the neutron source, the samples were set around the neutron source and were irradiated by neutrons of different energy depending on each sample position. The amount of helium produced in a sample was measured by Helium Atoms Measurement System at Kyushu University. The results of this work are in good agreement with other experimental data in the literature and also compared with the evaluated values in JENDL-3. (author)

  8. Iron

    Science.gov (United States)

    Iron is a mineral that our bodies need for many functions. For example, iron is part of hemoglobin, a protein which carries ... It helps our muscles store and use oxygen. Iron is also part of many other proteins and ...

  9. An intracranial aspergilloma with low signal on T2-weighted images corresponding to iron accumulation

    Energy Technology Data Exchange (ETDEWEB)

    Yamada, K. [Dept. of Radiology, Kyoto Prefectural Univ. of Medicine (Japan); Dept. of Radiology, Univ. of Maryland Medical Center, Baltimore MD (United States); Zoarski, G.H.; Rothman, M.I.; Zagardo, M.T. [Dept. of Radiology, Univ. of Maryland Medical Center, Baltimore MD (United States); Nishimura, T. [Dept. of Radiology, Kyoto Prefectural Univ. of Medicine (Japan); Sun, C.C.J. [Dept. of Pathology, Univ. of Maryland Medical Center, Baltimore MD (United States)

    2001-07-01

    We present a case of cerebral aspergillosis in an immunocompetent patient. The MRI signal characteristics were compared with the histologic findings. Irregular low-signal zones were demonstrated between the wall of the abscess and the central necrosis on T2-weighted images; the pathology specimen revealed concentrated iron in these transitional zones but no hemosiderin. Iron is an essential element for the growth of fungal hyphae. The low-signal zones may represent the areas where there was active proliferation of aspergillus, and the unique location of the low signal may be a helpful imaging characteristic for the diagnosis of an aspergillus abscess. (orig.)

  10. High relative air humidity influences mineral accumulation and growth in iron deficient soybean plants

    NARCIS (Netherlands)

    Roriz, M.; Carvalho, S.M.P.; Wilton Vasconcelos, M.

    2014-01-01

    Iron (Fe) deficiency chlorosis (IDC) in soybean results in severe yield losses. Cultivar selection is the most commonly used strategy to avoid IDC but there is a clear interaction between genotype and the environment; therefore, the search for quick and reliable tools to control this nutrient

  11. Zinc, copper, iron, and selenium levels in brain and liver of mice exposed to acrylonitrile.

    Science.gov (United States)

    Rongzhu, Lu; Suhua, Wang; Guangwei, Xing; Chunlan, Ren; Fangan, Han; Junjie, Jing; Aschner, Michael

    2009-07-01

    The mechanism of toxicity of acrylonitrile (AN) has not been fully defined. The research described herein was undertaken to investigate the possible effects of AN on the levels of metallic elements in liver and brain of mice. Thirty-two mice were randomly assigned to four separate groups and treated intraperitoneal (i.p.) once daily for 1 week. Mice in the control group received normal saline, and mice in the three exposure groups received 5, 10, or 20 mg AN/kg b.w. Samples of brain and liver were collected immediately after decapitation. Tissue levels of trace elements (zinc, copper, iron) were determined with flame atomic absorption spectrophotometer or double channel atomic fluorescence absorption spectrophotometer (selenium). Mean brain weights of AN-treated mice were increased as a function of dose compared to controls, but there was no significant change in the ratio of liver/body weight in the four groups. While mean brain zinc decreased as a function of AN dosage, mean liver zinc of the low-dose group significantly increased (p 0.05). Mean brain iron levels were significantly decreased in the middle-dose AN group (p < 0.05), but there were no consistent changes in liver iron. Tissue levels of selenium in brain and liver were similar for the control and AN treatment groups. AN induces significant and differential changes in the levels of zinc, copper, and iron in brain and liver. These changes likely play a pivotal role in mediating AN toxicity, most likely via changes in cellular redox status.

  12. MRI estimates of brain iron concentration in normal aging using quantitative susceptibility mapping.

    Science.gov (United States)

    Bilgic, Berkin; Pfefferbaum, Adolf; Rohlfing, Torsten; Sullivan, Edith V; Adalsteinsson, Elfar

    2012-02-01

    Quantifying tissue iron concentration in vivo is instrumental for understanding the role of iron in physiology and in neurological diseases associated with abnormal iron distribution. Herein, we use recently-developed Quantitative Susceptibility Mapping (QSM) methodology to estimate the tissue magnetic susceptibility based on MRI signal phase. To investigate the effect of different regularization choices, we implement and compare ℓ1 and ℓ2 norm regularized QSM algorithms. These regularized approaches solve for the underlying magnetic susceptibility distribution, a sensitive measure of the tissue iron concentration, that gives rise to the observed signal phase. Regularized QSM methodology also involves a pre-processing step that removes, by dipole fitting, unwanted background phase effects due to bulk susceptibility variations between air and tissue and requires data acquisition only at a single field strength. For validation, performances of the two QSM methods were measured against published estimates of regional brain iron from postmortem and in vivo data. The in vivo comparison was based on data previously acquired using Field-Dependent Relaxation Rate Increase (FDRI), an estimate of MRI relaxivity enhancement due to increased main magnetic field strength, requiring data acquired at two different field strengths. The QSM analysis was based on susceptibility-weighted images acquired at 1.5 T, whereas FDRI analysis used Multi-Shot Echo-Planar Spin Echo images collected at 1.5 T and 3.0 T. Both datasets were collected in the same healthy young and elderly adults. The in vivo estimates of regional iron concentration comported well with published postmortem measurements; both QSM approaches yielded the same rank ordering of iron concentration by brain structure, with the lowest in white matter and the highest in globus pallidus. Further validation was provided by comparison of the in vivo measurements, ℓ1-regularized QSM versus FDRI and ℓ2-regularized QSM

  13. Accumulation of magnetic iron oxide nanoparticles coated with variably sized polyethylene glycol in murine tumors

    DEFF Research Database (Denmark)

    Larsen, Esben Kjær Unmack; Nielsen, Thomas; Wittenborn, Thomas

    2012-01-01

    Iron oxide nanoparticles have found widespread applications in different areas including cell separation, drug delivery and as contrast agents. Due to water insolubility and stability issues, nanoparticles utilized for biological applications require coatings such as the commonly employed...... polyethylene glycol (PEG). Despite its frequent use, the influence of PEG coatings on the physicochemical and biological properties of iron nanoparticles has hitherto not been studied in detail. To address this, we studied the effect of 333–20 000 Da PEG coatings that resulted in larger hydrodynamic size......, lower surface charge, longer circulation half-life, and lower uptake in macrophage cells when the particles were coated with high molecular weight (Mw) PEG molecules. By use of magnetic resonance imaging, we show coating-dependent in vivo uptake in murine tumors with an optimal coating Mw of 10 000 Da...

  14. Role of blood-brain barrier P-glycoprotein in limiting brain accumulation and sedative side-effects of asimadoline, a peripherally acting analgaesic drug

    NARCIS (Netherlands)

    Jonker, JW; Wagenaar, E; van Deemter, L; Gottschlich, R; Bender, HM; Dasenbrock, J; Schinkel, AH

    1 Studies with knockout mice lacking mdrla P-glycoprotein (P-gp) have previously shown that blood-brain barrier P-gp is important in preventing the accumulation of several drugs in the brain. 2 Asimadoline (EMD 61753) is a peripherally selective kappa-opioid receptor agonist which is under

  15. Exogenous iron redistribution between brain and spleen after the administration of the 57Fe3O4 ferrofluid into the ventricle of the brain

    Science.gov (United States)

    Gabbasov, Raul; Polikarpov, Dmitry; Cherepanov, Valery; Chuev, Michael; Mischenko, Ilya; Loginiva, Nadezhda; Loseva, Elena; Nikitin, Maxim; Panchenko, Vladislav

    2017-04-01

    Iron clearance pathways after the injection of 57Fe3O4-based dextran-stabilized ferrofluid into the brain ventricles were studied by Mössbauer spectroscopy and histologically. The nanoparticles appeared in spleen tissues within 3 h after transcranial injection. We separated and independently estimated concentrations of iron encapsulated in nanoparticles and iron encapsulated in proteins in the all rat organs. It was found that the dextran coated initial nanoparticles of the ferrofluid disintegrated in the brain into separate superparamagnetic nanoparticles within a week after the injection.The nanoparticles completely exited from the brain in a few weeks. The exogenous iron appeared in the spleen in 3 h after the injection and remained in the spleen for more than month. The appearance of additional component in Mössbauer spectra of spleen samples revealed a fundamental difference in the mechanisms of processing of iron nanoparticles in this organ, which was also confirmed by histological examination.

  16. Impaired myelination and reduced brain ferric iron in the mouse model of mucolipidosis IV

    Directory of Open Access Journals (Sweden)

    Yulia Grishchuk

    2015-12-01

    Full Text Available Mucolipidosis type IV (MLIV is a lysosomal storage disease caused by mutations in the MCOLN1 gene, which encodes the lysosomal transient receptor potential ion channel mucolipin-1 (TRPML1. MLIV causes impaired motor and cognitive development, progressive loss of vision and gastric achlorhydria. How loss of TRPML1 leads to severe psychomotor retardation is currently unknown, and there is no therapy for MLIV. White matter abnormalities and a hypoplastic corpus callosum are the major hallmarks of MLIV brain pathology. Here, we report that loss of TRPML1 in mice results in developmental aberrations of brain myelination as a result of deficient maturation and loss of oligodendrocytes. Defective myelination is evident in Mcoln1−/− mice at postnatal day 10, an active stage of postnatal myelination in the mouse brain. Expression of mature oligodendrocyte markers is reduced in Mcoln1−/− mice at postnatal day 10 and remains lower throughout the course of the disease. We observed reduced Perls' staining in Mcoln1−/− brain, indicating lower levels of ferric iron. Total iron content in unperfused brain is not significantly different between Mcoln1−/− and wild-type littermate mice, suggesting that the observed maturation delay or loss of oligodendrocytes might be caused by impaired iron handling, rather than by global iron deficiency. Overall, these data emphasize a developmental rather than a degenerative disease course in MLIV, and suggest that there should be a stronger focus on oligodendrocyte maturation and survival to better understand MLIV pathogenesis and aid treatment development.

  17. Helicobacter pylori Infection Induces Anemia, Depletes Serum Iron Storage, and Alters Local Iron-Related and Adult Brain Gene Expression in Male INS-GAS Mice.

    Science.gov (United States)

    Burns, Monika; Muthupalani, Sureshkumar; Ge, Zhongming; Wang, Timothy C; Bakthavatchalu, Vasudevan; Cunningham, Catriona; Ennis, Kathleen; Georgieff, Michael; Fox, James G

    2015-01-01

    Iron deficiency anemia (IDA) affects > 500 million people worldwide, and is linked to impaired cognitive development and function in children. Helicobacter pylori, a class 1 carcinogen, infects about half of the world's population, thus creating a high likelihood of overlapping risk. This study determined the effect of H. pylori infection on iron homeostasis in INS-GAS mice. Two replicates of INS-GAS/FVB male mice (n = 9-12/group) were dosed with H. pylori (Hp) strain SS1 or sham dosed at 6-9 weeks of age, and were necropsied at 27-29 weeks of age. Hematologic and serum iron parameters were evaluated, as was gene expression in gastric and brain tissues. Serum ferritin was lower in Hp SS1-infected mice than uninfected mice (p brain expression of tyrosine hydroxylase (Th) (p = 0.02). Expression of iron-responsive genes involved in myelination (myelin basic protein (Mbp) and proteolipid protein 2 (Plp2)) was downregulated in infected mice (p = 0.001 and p = 0.02). Expression of synaptic plasticity markers (brain derived neurotrophic factor 3 (Bdnf3), Psd95 (a membrane associated guanylate kinase), and insulin-like growth factor 1 (Igf1)) was also downregulated in Hp SS1-infected mice (p = 0.09, p = 0.04, p = 0.02 respectively). Infection of male INS-GAS mice with Hp SS1, without concurrent dietary iron deficiency, depleted serum ferritin, deregulated gastric and hepatic expression of iron regulatory genes, and altered iron-dependent neural processes. The use of Hp SS1-infected INS-GAS mice will be an appropriate animal model for further study of the effects of concurrent H. pylori infection and anemia on iron homeostasis and adult iron-dependent brain gene expression.

  18. Blood-brain barrier to peptides: (/sup 3/H)gonadotropin-releasing hormone accumulation by eighteen regions of the rat brain and by anterior pituitary

    Energy Technology Data Exchange (ETDEWEB)

    Ermisch, A.; Ruehle, H.J. (Karl-Marx-Universitaet, Leipzig (German Democratic Republic). Sektion Biowissenschaften); Klauschenz, E.; Kretzschmar, R. (Akademie der Wissenschaften der DDR, Berlin. Inst. fuer Wirkstofforschung)

    1984-01-01

    After intracarotid injection of (/sup 3/H)gonadotropin-releasing hormone ((/sup 3/H)GnRH) the mean accumulation of radioactivity per unit wet weight of 18 brain samples investigated and the anterior pituitary was 0.38 +- 0.11% g/sup -1/ of the injected tracer dose. This indicates a low but measurable brain uptake of the peptide. The brain uptake of (/sup 3/H)GnRH in blood-brain barrier (BBB)-protected regions is 5% of that of separately investigated (/sup 3/H)OH. In BBB-free regions the accumulation of radioactivity was more than 25-fold higher than in BBB-protected regions. The accumulation of (/sup 3/H)GnRH among regions with BBB varies less than among regions with leaky endothelia. The data presented for (/sup 3/H)GnRH are similar to those for other peptides so far investigated.

  19. Iron

    DEFF Research Database (Denmark)

    Hansen, Jakob Bondo; Moen, I W; Mandrup-Poulsen, T

    2014-01-01

    The interest in the role of ferrous iron in diabetes pathophysiology has been revived by recent evidence of iron as an important determinant of pancreatic islet inflammation and as a biomarker of diabetes risk and mortality. The iron metabolism in the β-cell is complex. Excess free iron is toxic......, but at the same time, iron is required for normal β-cell function and thereby glucose homeostasis. In the pathogenesis of diabetes, iron generates reactive oxygen species (ROS) by participating in the Fenton chemistry, which can induce oxidative damage and apoptosis. The aim of this review is to present...... and discuss recent evidence, suggesting that iron is a key pathogenic factor in both type 1 and type 2 diabetes with a focus on inflammatory pathways. Pro-inflammatory cytokine-induced β-cell death is not fully understood, but may include iron-induced ROS formation resulting in dedifferentiation by activation...

  20. Magnesium and iron deficiencies alter Cd accumulation in Salix viminalis L.

    Science.gov (United States)

    Borišev, M; Pajević, S; Nikolić, N; Orlović, S; Župunski, M; Pilipović, A; Kebert, M

    2016-01-01

    Evidence exists that Cd and certain nutrient elements, such as Fe and Mg, could share similar mechanisms of plant uptake and accumulation. Here we report that Mg and Fe deficiency in mature plants of Salix viminalis, grown in hydroponic solutions containing 5 µg ml(-1) of Cd, caused a significant increase in Cd accumulation in roots, stems and leaves. Cd (µg g(-1) dry weight) was determined following three treatments: 1) Cd treatment in complete nutrient solution; 2) Cd treatment with Fe deficiency; and 3) Cd treatment with Mg deficiency, yielding, respectively: in young leaves (65.3, 76.1, and 92.2), mature leaves (51.5 to 76.3 and 87.1), upper stems (80.6, 116.8, and 130.6) lower stems (67.2, 119, and 102.3), roots (377.1, 744.8, and 442,5). Our results suggest that Cd utilizes the same uptake and transport pathways as Mg and Fe. Evidence exists that Mg and Fe uptake and translocation could be further facilitated by plants as an adaptive response to deficiency of these elements. Such physiological reaction could additionally stimulate Cd accumulation. Although Cd uptake was mostly confined in roots, high Cd content in aerial plant parts (51.5-130.6 µg g(-1)) indicates that the analysed Salix viminalis genotype is suitable for phytoextraction.

  1. Iron and Mechanisms of Neurotoxicity

    Directory of Open Access Journals (Sweden)

    Gabriela A. Salvador

    2011-01-01

    Full Text Available The accumulation of transition metals (e.g., copper, zinc, and iron and the dysregulation of their metabolism are a hallmark in the pathogenesis of several neurodegenerative diseases. This paper will be focused on the mechanism of neurotoxicity mediated by iron. This metal progressively accumulates in the brain both during normal aging and neurodegenerative processes. High iron concentrations in the brain have been consistently observed in Alzheimer's (AD and Parkinson's (PD diseases. In this connection, metalloneurobiology has become extremely important in establishing the role of iron in the onset and progression of neurodegenerative diseases. Neurons have developed several protective mechanisms against oxidative stress, among them, the activation of cellular signaling pathways. The final response will depend on the identity, intensity, and persistence of the oxidative insult. The characterization of the mechanisms mediating the effects of iron-induced increase in neuronal dysfunction and death is central to understanding the pathology of a number of neurodegenerative disorders.

  2. Slow accumulation of psychotropic substances in the human brain. Relationship to therapeutic latency of neuroleptic and antidepressant drugs?

    Science.gov (United States)

    Kornhuber, J; Retz, W; Riederer, P

    1995-01-01

    The mechanism of therapeutic latency of antidepressant and neuroleptic drugs is not clearly understood. Current hypotheses include slow adaptive processes after fast access to primary drug targets. Here, we present a hypothesis explaining therapeutic latency by slow accumulation of the drugs in acidic intracellular compartments. We have studied the pharmacokinetics of amantadine, a lysosomotropic model substance. It's fast therapeutic response is mediated by fast access to cell surface receptors. However, it slowly accumulates intracellularly in human brain tissue. Half-maximal and plateau concentrations are reached after 8 and at least 70 days of treatment, respectively. The concentration in brain tissue relative to CSF and serum is about 20:1. The high storage capacity of brain tissue is probably related to lysosomotropic properties of amantadine. This means that amantadine, as other lysosomotropic substances, is trapped by protonation in acidic intracellular compartments and may disturb biochemical processes that require an acidic milieu, such as the proton-driven transport of monoamines into synaptic vesicles. The mean daily oral dose of amantadine is low compared to the high storage capacity of brain and other tissues thus explaining the slow accumulation. Many psychotropic drugs including antidepressant and neuroleptic substances also have lysosomotropic properties. A slow accumulation in brain tissue is therefore likely for many antidepressant and neuroleptic drugs and has been directly demonstrated for fluoxetine. While lysosomotropism alone is not a sufficient explanation for antidepressant or neuroleptic properties of a certain drug, it contributes to high storage capacity and slow accumulation in brain tissue and results in disturbances of several biochemical processes. Slow accumulation in brain tissue might be related to the therapeutic latency of neuroleptic and antidepressant drugs.

  3. Perinatal Iron and Copper Deficiencies Alter Neonatal Rat Circulating and Brain Thyroid Hormone Concentrations

    OpenAIRE

    Bastian, Thomas W.; Prohaska, Joseph R.; Georgieff, Michael K; Anderson, Grant W.

    2010-01-01

    Copper (Cu), iron (Fe), and iodine/thyroid hormone (TH) deficiencies lead to similar defects in late brain development, suggesting that these micronutrient deficiencies share a common mechanism contributing to the observed derangements. Previous studies in rodents (postweanling and adult) and humans (adolescent and adult) indicate that Cu and Fe deficiencies affect the hypothalamic-pituitary-thyroid axis, leading to altered TH status. Importantly, however, relationships between Fe and Cu defi...

  4. Temporal course of cerebrospinal fluid dynamics and amyloid accumulation in the aging rat brain from three to thirty months

    Directory of Open Access Journals (Sweden)

    Chiu Catherine

    2012-01-01

    Full Text Available Abstract Background Amyloid accumulation in the brain parenchyma is a hallmark of Alzheimer's disease (AD and is seen in normal aging. Alterations in cerebrospinal fluid (CSF dynamics are also associated with normal aging and AD. This study analyzed CSF volume, production and turnover rate in relation to amyloid-beta peptide (Aβ accumulation in the aging rat brain. Methods Aging Fischer 344/Brown-Norway hybrid rats at 3, 12, 20, and 30 months were studied. CSF production was measured by ventriculo-cisternal perfusion with blue dextran in artificial CSF; CSF volume by MRI; and CSF turnover rate by dividing the CSF production rate by the volume of the CSF space. Aβ40 and Aβ42 concentrations in the cortex and hippocampus were measured by ELISA. Results There was a significant linear increase in total cranial CSF volume with age: 3-20 months (p p p p -1 to 12 months (11.30 day-1 and then a decrease to 20 months (10.23 day-1 and 30 months (6.62 day-1. Aβ40 and Aβ42 concentrations in brain increased from 3-30 months (p Conclusions In young rats there is no correlation between CSF turnover and Aβ brain concentrations. After 12 months, CSF turnover decreases as brain Aβ continues to accumulate. This decrease in CSF turnover rate may be one of several clearance pathway alterations that influence age-related accumulation of brain amyloid.

  5. Influence of dissolved inorganic carbon and calcium on gas formation and accumulation in iron permeable reactive barriers.

    Science.gov (United States)

    Ruhl, Aki S; Weber, Anne; Jekel, Martin

    2012-11-01

    Uncertainties in long-term reactivity and gas accumulation in Fe(0) permeable reactive barriers still hinder a broad application of this groundwater remediation technology. In this study long-term column experiments were conducted under varying geochemical conditions. Generation of hydrogen by anaerobic corrosion in Fe(0) reactive filters was mainly influenced by the mass flux of dissolved inorganic carbon. Both increased concentrations and volume flows led to a substantial rise in gas generation but only to slight differences of gas accumulation within the pores of the reactive filter. Comparisons of columns with different lengths showed higher averaged corrosion rates in the shorter and lower corrosion rates in the longer columns. Calcium in conjunction with dissolved inorganic carbon formed compact and localized aragonite minerals, while in the absence of calcium chukanovite dominated, which covered and passivated the reactive surface to a higher extent. Magnetite was the major crystalline corrosion product in the absence of carbonate and no decline in long term corrosion rates was observed within up to 700 days of operation. Total gas yields of columns were restricted by passivation and approached a volume of approximately 13.5 mL/g granulated cast iron. Copyright © 2012 Elsevier B.V. All rights reserved.

  6. Accumulated Source Imaging of Brain Activity with Both Low and High-Frequency Neuromagnetic Signals

    Directory of Open Access Journals (Sweden)

    Jing eXiang

    2014-05-01

    Full Text Available Recent studies have revealed the importance of high-frequency brain signals (>70 Hz. One challenge of high-frequency signal analysis is that the size of time-frequency representation of high-frequency brain signals could be larger than 1 terabytes (TB, which is beyond the upper limits of a typical computer workstation’s memory (<196 GB. The aim of the present study is to develop a new method to provide greater sensitivity in detecting high-frequency magnetoencephalography (MEG signals in a single automated and versatile interface, rather than the more traditional, time-intensive visual inspection methods, which may take up to several days. To address the aim, we developed a new method, accumulated source imaging, defined as the volumetric summation of source activity over a period of time. This method analyzes signals in both low- (1~70 Hz and high-frequency (70~200 Hz ranges at source levels. To extract meaningful information from MEG signals at sensor space, the signals were decomposed to channel-cross-channel matrix (CxC representing the spatiotemporal patterns of every possible sensor-pair. A new algorithm was developed and tested by calculating the optimal CxC and source location-orientation weights for volumetric source imaging, thereby minimizing multi-source interference and reducing computational cost. The new method was implemented in C/C++ and tested with MEG data recorded from clinical epilepsy patients. The results of experimental data demonstrated that accumulated source imaging could effectively summarize and visualize MEG recordings within 12.7 hours by using approximately 10 GB of computer memory. In contrast to the conventional method of visually identifying multi-frequency epileptic activities that traditionally took 2-3 days and used 1-2 TB storage, the new approach can quantify epileptic abnormalities in both low- and high-frequency ranges at source levels, using much less time and computer memory.

  7. High relative air humidity influences mineral accumulation and growth in iron deficient soybean plants.

    Science.gov (United States)

    Roriz, Mariana; Carvalho, Susana M P; Vasconcelos, Marta W

    2014-01-01

    Iron (Fe) deficiency chlorosis (IDC) in soybean results in severe yield losses. Cultivar selection is the most commonly used strategy to avoid IDC but there is a clear interaction between genotype and the environment; therefore, the search for quick and reliable tools to control this nutrient deficiency is essential. Several studies showed that relative humidity (RH) may influence the long distance transport of mineral elements and the nutrient status of plants. Thus, we decided to analyze the response of an "Fe-efficient" (EF) and an "Fe-inefficient" (INF) soybean accession grown under Fe-sufficient and deficient conditions under low (60%) and high (90%) RH, evaluating morphological, and physiological parameters. Furthermore, the mineral content of different plant organs was analyzed. Our results showed beneficial effects of high RH in alleviating IDC symptoms as seen by increased SPAD values, higher plant dry weight (DW), increased plant height, root length, and leaf area. This positive effect of RH in reducing IDC symptoms was more pronounced in the EF accession. Also, Fe content in the different plant organs of the EF accession grown under deficient conditions increased with RH. The lower partitioning of Fe to roots and stems of the EF accessions relative to dry matter also supported our hypothesis, suggesting a greater capacity of this accession in Fe translocation to the aerial parts under Fe deficient conditions, when grown under high RH.

  8. High relative air humidity influences mineral accumulation and growth in iron deficient soybean plants

    Directory of Open Access Journals (Sweden)

    Mariana eRoriz

    2014-12-01

    Full Text Available Iron (Fe deficiency chlorosis (IDC in soybean results in severe yield losses. Cultivar selection is the most commonly used strategy to avoid IDC but there is a clear interaction between genotype and the environment; therefore, the search for quick and reliable tools to control this nutrient deficiency is essential. Several studies showed that relative humidty (RH may influence the long distance transport of mineral elements and the nutrient status of plants. Thus, we decided to analyze the response of an ‘Fe-efficient’ (EF and an ‘Fe-inefficient’ (INF soybean accession grown under Fe-sufficient and deficient conditions under low (60% and high (90% RH, evaluating morphological and physiological parameters. Furthermore, the mineral content of different plant organs was analyzed. Our results showed beneficial effects of high RH in alleviating IDC symptoms as seen by increased SPAD values, higher plant dry weight, increased plant height, root length and leaf area. This positive effect of RH in reducing IDC symptoms was more pronounced in the EF accession. Also, Fe content in the different plant organs of the EF accession grown under deficient conditions increased with RH. The lower partitioning of Fe to roots and stems of the EF accessions relative to dry matter also supported our hypothesis, suggesting a greater capacity of this accession in Fe translocation to the aerial parts under Fe deficient conditions, when grown under high RH.

  9. Brain copper, iron, magnesium, zinc, calcium, sulfur and phosphorus storage in Wilson's disease.

    Science.gov (United States)

    Faa, G; Lisci, M; Caria, M P; Ambu, R; Sciot, R; Nurchi, V M; Silvagni, R; Diaz, A; Crisponi, G

    2001-01-01

    Wilson's disease (WD) is an inherited disorder of copper metabolism characterised by juvenile liver cirrhosis and by neurological symptoms. Copper levels in brain in WD have been reported to be 10 to 15 fold normal values, depending on the different brain regions. Being very few data on copper distribution in central nervous system in WD available, it seemed of interest to study the concentration of copper and of other trace elements (Zn, P, Mg, Ca, Fe and S) in the brain of a patient died for WD. a 56 year old woman affected by WD was admitted to our hospital with signs of hepatic failure and died few days later. At autopsy, a brain slice extending from the left to the right hemisphere was divided in 28 samples. On each sample Copper, Iron, Magnesium, Phosphorus, Sulphur, Zinc and Calcium were determined by Induced Coupled Plasma Atomic Emission Spectroscopy. the mean concentration of copper, ranging from 88 to 158 microg/g of dry tissue in all the brain specimens was higher than literature reference values, while that of the other tested elements was considerably lower. 1) In the brain of WD patient examined the status of trace elements was extensively altered. Further studies are necessary to correlate the concentration of trace elements with pathological lesions and with clinical pictures. 2) The elements considered in our study showed an uneven distribution in different brain areas.

  10. Parkinson's Disease: The Mitochondria-Iron Link

    Science.gov (United States)

    Carrasco, Carlos M.; Núñez, Marco T.

    2016-01-01

    Mitochondrial dysfunction, iron accumulation, and oxidative damage are conditions often found in damaged brain areas of Parkinson's disease. We propose that a causal link exists between these three events. Mitochondrial dysfunction results not only in increased reactive oxygen species production but also in decreased iron-sulfur cluster synthesis and unorthodox activation of Iron Regulatory Protein 1 (IRP1), a key regulator of cell iron homeostasis. In turn, IRP1 activation results in iron accumulation and hydroxyl radical-mediated damage. These three occurrences—mitochondrial dysfunction, iron accumulation, and oxidative damage—generate a positive feedback loop of increased iron accumulation and oxidative stress. Here, we review the evidence that points to a link between mitochondrial dysfunction and iron accumulation as early events in the development of sporadic and genetic cases of Parkinson's disease. Finally, an attempt is done to contextualize the possible relationship between mitochondria dysfunction and iron dyshomeostasis. Based on published evidence, we propose that iron chelation—by decreasing iron-associated oxidative damage and by inducing cell survival and cell-rescue pathways—is a viable therapy for retarding this cycle. PMID:27293957

  11. Chronic exposure of tilapia (Oreochromis niloticus) to iron oxide nanoparticles: Effects of particle morphology on accumulation, elimination, hematology and immune responses

    Science.gov (United States)

    Ates, Mehmet; Demir, Veysel; Arslan, Zikri; Kaya, Hasan; Yılmaz, Sevdan; Camas, Mustafa

    2016-01-01

    Effects of chronic exposure to alpha and gamma iron oxide nanoparticles (α-Fe2O3 and γ-Fe2O3 NPs) were investigated through exposure of tilapia (Oreochromis niloticus) to 0.1, 0.5 and 1.0 mg/L (9.2×10−4, 4.6×10−3 and 9.2×10−3 mM) aqueous suspensions for 60 days. Fish were then transferred to NP-free freshwater and allowed to eliminate ingested NPs for 30 days. The organs, including gills, liver, kidney, intestine, brain, spleen, and muscle tissue of the fish were analyzed to determine the accumulation, physiological distribution and elimination of the Fe2O3 NPs. Largest accumulation occurred in spleen followed by intestine, kidney, liver, gills, brain and muscle tissue. Fish exposed to γ-Fe2O3 NPs possessed significantly higher Fe in all organs. Accumulation in spleen was fast and independent of NP concentration reaching to maximum levels by the end of the first sampling period (30th day). Dissolved Fe levels in water were very negligible ranging at 4–6 μg/L for α-Fe2O3 and 17–21 μg/L for γ-Fe2O3 NPs (for 1 mg/L suspensions). Despite that, Fe levels in gills and brain reflect more dissolved Fe accumulation from metastable γ-Fe2O3 polymorph. Ingested NPs cleared from the organs completely within 30-day elimination period, except the liver and spleen. Liver contained about 31% of α- and 46% of γ-Fe2O3, while spleen retained about 62% of α- and 35% of the γ-polymorph. No significant disturbances were observed in hematological parameters, including hemoglobin, hematocrit, red blood cell and white blood cell counts (p > 0.05). Serum glucose (GLU) levels decreased in treatments exposed to 1.0 mg/L of γ-Fe2O3 NPs at day 30 (p 0.05), but increased significantly within elimination period due to mobilization of ingested NPs from liver and spleen to blood. Though respiratory burst activity was not affected (p > 0.05), lysozyme activity (LA) was suppressed suggesting an immunosuppressive effects from both Fe2O3 NPs (p < 0.05). In contrast

  12. Accumulation of Mercury, Cadmium, Tin, Nickel, iron and Zinc in canned tuna from Khuzestan Province

    Directory of Open Access Journals (Sweden)

    M Velayatzadeh

    2014-11-01

    Full Text Available Toxicity of heavy metals has led to numerous studies on the accumulation of these elements in fish and fishery products such as canned products. The objective of the present study was to determine the concentrations of Hg, Cd, Sn, Zn, Ni, Fe in canned tuna fish from of Khuzestan Provinces. A total number of 54 tuna fish cans from three brands (A, B and C was collected from Ahvaz retails. The samples were subjected to dry digestion and the concentrations of the heavy metals were measured using Atomic Absorption Spectrophotometer Perkin Elmer 4100. In this study, no significant difference was observed between the concentrations of heavy metals in three various samples (P>0.05. The mean concentrations of Hg, Cd, Ni Sn, Zn and Fe in group C samples were determined at 0.048±0.007, 0.297±0.053, 0.171±0.031, 0.062±0.012, 5.36±0.82, 7.63±0.04 mg/Kg. Moreover, the highest level of Cd, Ni and Fe concentrations was observed in group C samples. In comparison with WHO, FAO and FDA standards, concentration of Ni, Sn, Hg and Zn was found lower. Meanwhile, the concentration of Cd was estimated higher than WHO, NHMRC and UKMAFF limits.

  13. Differential Tissue Accumulation of Copper, Iron, and Zinc in Bycatch Fish from the Mexican Pacific.

    Science.gov (United States)

    Spanopoulos-Zarco, P; Ruelas-Inzunza, J; Aramburo-Moran, I S; Bojórquez-Leyva, H; Páez-Osuna, F

    2017-03-01

    In order to ascertain if Cu, Fe, and Zn are differentially accumulated in fish tissues, metal concentrations were measured in the muscle and liver of bycatch fish from the states of Sinaloa (189 specimens, 7 species) and Guerrero (152 individuals, 8 species) in the Mexican Pacific Coast during March and November 2011. Additionally, metal levels were compared with the maximum allowable limits set by international legislation and contrasted with similar ichthyofauna from other regions. Liver had more elevated concentrations of Cu (Sinaloa 28.3, Guerrero 16.3 μg g-1), Fe (Sinaloa 1098, Guerrero 636 μg g-1), and Zn (Sinaloa 226, Guerrero 186 μg g-1) than the muscle in fish from both studied areas. The relative abundances of analyzed metals in both tissues was Fe > Zn > Cu. As far as limits set by international legislation (Australia, India, New Zealand, Zambia), measured concentrations of Cu in the edible portion of fish were not found to be above the set values. In the case of Zn, the maximum allowable limits set by international legislation were exceeded by the Peruvian mojarra Diapterus peruvianus from Guerrero state (Mexican Pacific). No limits exist for Fe in the edible portion of fishery products in the national and international legislations.

  14. Exogenous Melatonin Improves Plant Iron Deficiency Tolerance via Increased Accumulation of Polyamine-Mediated Nitric Oxide

    Directory of Open Access Journals (Sweden)

    Cheng Zhou

    2016-10-01

    Full Text Available Melatonin has recently been demonstrated to play important roles in the regulation of plant growth, development, and abiotic and biotic stress responses. However, the possible involvement of melatonin in Fe deficiency responses and the underlying mechanisms remained elusive in Arabidopsis thaliana. In this study, Fe deficiency quickly induced melatonin synthesis in Arabidopsis plants. Exogenous melatonin significantly increased the soluble Fe content of shoots and roots, and decreased the levels of root cell wall Fe bound to pectin and hemicellulose, thus alleviating Fe deficiency-induced chlorosis. Intriguingly, melatonin treatments induced a significant increase of nitric oxide (NO accumulation in roots of Fe-deficient plants, but not in those of polyamine-deficient (adc2-1 and d-arginine-treated plants. Moreover, the melatonin-alleviated leaf chlorosis was blocked in the polyamine- and NO-deficient (nia1nia2noa1 and c-PTIO-treated plants, and the melatonin-induced Fe remobilization was largely inhibited. In addition, the expression of some Fe acquisition-related genes, including FIT1, FRO2, and IRT1 were significantly up-regulated by melatonin treatments, whereas the enhanced expression of these genes was obviously suppressed in the polyamine- and NO-deficient plants. Collectively, our results provide evidence to support the view that melatonin can increase the tolerance of plants to Fe deficiency in a process dependent on the polyamine-induced NO production under Fe-deficient conditions.

  15. Overexpression of ZmIRT1 and ZmZIP3 Enhances Iron and Zinc Accumulation in Transgenic Arabidopsis.

    Directory of Open Access Journals (Sweden)

    Suzhen Li

    Full Text Available Iron and zinc are important micronutrients for both the growth and nutrient availability of crop plants, and their absorption is tightly controlled by a metal uptake system. Zinc-regulated transporters, iron-regulated transporter-like proteins (ZIP, is considered an essential metal transporter for the acquisition of Fe and Zn in graminaceous plants. Several ZIPs have been identified in maize, although their physiological function remains unclear. In this report, ZmIRT1 was shown to be specifically expressed in silk and embryo, whereas ZmZIP3 was a leaf-specific gene. Both ZmIRT1 and ZmZIP3 were shown to be localized to the plasma membrane and endoplasmic reticulum. In addition, transgenic Arabidopsis plants overexpressing ZmIRT1 or ZmZIP3 were generated, and the metal contents in various tissues of transgenic and wild-type plants were examined based on ICP-OES and Zinpyr-1 staining. The Fe and Zn concentration increased in roots and seeds of ZmIRT1-overexpressing plants, while the Fe content in shoots decreased. Overexpressing ZmZIP3 enhanced Zn accumulation in the roots of transgenic plants, while that in shoots was repressed. In addition, the transgenic plants showed altered tolerance to various Fe and Zn conditions compared with wild-type plants. Furthermore, the genes associated with metal uptake were stimulated in ZmIRT1 transgenic plants, while those involved in intra- and inter- cellular translocation were suppressed. In conclusion, ZmIRT1 and ZmZIP3 are functional metal transporters with different ion selectivities. Ectopic overexpression of ZmIRT1 may stimulate endogenous Fe uptake mechanisms, which may facilitate metal uptake and homeostasis. Our results increase our understanding of the functions of ZIP family transporters in maize.

  16. Soybean genotypic difference in growth, nutrient accumulation and ultrastructure in response to manganese and iron supply in solution culture.

    Science.gov (United States)

    Izaguirre-Mayoral, M L; Sinclair, T R

    2005-07-01

    The objective of this research was to characterize the physiology and cell ultrastructure of two soybean genotypes subjected to nutrient solutions with increasing concentrations of manganese (Mn) at two contrasting iron (Fe) concentrations. Genotypes 'PI227557' and 'Biloxi' were selected based on their distinctly different capacities to accumulate Mn and Fe. * Bradyrhizobium-inoculated plants were grown in hydroponic cultures in a greenhouse. Nutrient solutions were supplied with Mn concentrations ranging from 0.3 to 90 microm, at either 5 or 150 microm Fe as FeEDTA. * For both genotypes and at both Fe concentrations, Mn concentrations from 6.6 to 50 microm did not affect shoot, root and nodule mass, or leaf and nodule ureide concentration. Mn concentrations of 70 and 90 microm did not result in visible toxicity symptoms, but hindered growth and nodulation of 'Biloxi'. An Mn concentration of 0.3 microm was, however, deleterious to growth and nodulation for both genotypes, and caused an accumulation of ureides in leaves and major alterations in the ultrastructure of chloroplasts, nuclei and mitochondria, regardless of the Fe concentration. In 'PI227557', there was also a proliferation of Golgi apparatus and endoplasmic reticulum in the cytoplasm of leaf cells, and nodules showed disrupted symbiosomes lacking poly-beta-hydroxybutirate grains concomitantly with a proliferation of endoplasmic reticulum as well as arrested bacterial division. At 15 microm Fe, ferritin-like crystals were formed in the lumen of chloroplasts of 'PI227557' plants. For both genotypes, there was an antagonism between the Fe and Mn concentrations in leaves, the higher values of both microelements being detected in 'PI227557'. The absence of any detectable relationship between Fe or Mn and zinc, phosphorus and copper concentrations in leaves ruled out those micronutrients as relevant for Mn and Fe nutrition in soybeans. * The results confirmed the greater capacity of 'PI227557' for Mn and Fe

  17. MicroRNA miR-29 controls a compensatory response to limit neuronal iron accumulation during adult life and aging.

    Science.gov (United States)

    Ripa, Roberto; Dolfi, Luca; Terrigno, Marco; Pandolfini, Luca; Savino, Aurora; Arcucci, Valeria; Groth, Marco; Terzibasi Tozzini, Eva; Baumgart, Mario; Cellerino, Alessandro

    2017-02-13

    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. 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. Mechanicistically, we identified Ireb2 (a master gene for intracellular iron delivery that encodes for IRP2 protein), as a novel miR-29 target. MiR-29 is induced by iron loading and, in turn, it reduces IRP2 expression in vivo, therefore limiting intracellular iron delivery in neurons. Genetically modified fish with neuro-specific miR-29 deficiency exhibit increased levels of IRP2 and transferrin receptor, increased iron content, and oxidative stress. Our results demonstrate that age-dependent miR-29 upregulation is an adaptive mechanism that counteracts the expression of some aging-related phenotypes and its anti-aging activity is primarily exerted by regulating intracellular iron homeostasis limiting excessive iron-exposure in neurons.

  18. Lactoferrin conjugated iron oxide nanoparticles for targeting brain glioma cells in magnetic particle imaging

    Science.gov (United States)

    Tomitaka, Asahi; Arami, Hamed; Gandhi, Sonu; Krishnan, Kannan M.

    2015-10-01

    Magnetic Particle Imaging (MPI) is a new real-time imaging modality, which promises high tracer mass sensitivity and spatial resolution directly generated from iron oxide nanoparticles. In this study, monodisperse iron oxide nanoparticles with median core diameters ranging from 14 to 26 nm were synthesized and their surface was conjugated with lactoferrin to convert them into brain glioma targeting agents. The conjugation was confirmed with the increase of the hydrodynamic diameters, change of zeta potential, and Bradford assay. Magnetic particle spectrometry (MPS), performed to evaluate the MPI performance of these nanoparticles, showed no change in signal after lactoferrin conjugation to nanoparticles for all core diameters, suggesting that the MPI signal is dominated by Néel relaxation and thus independent of hydrodynamic size difference or presence of coating molecules before and after conjugations. For this range of core sizes (14-26 nm), both MPS signal intensity and spatial resolution improved with increasing core diameter of nanoparticles. The lactoferrin conjugated iron oxide nanoparticles (Lf-IONPs) showed specific cellular internalization into C6 cells with a 5-fold increase in MPS signal compared to IONPs without lactoferrin, both after 24 h incubation. These results suggest that Lf-IONPs can be used as tracers for targeted brain glioma imaging using MPI.

  19. Subcellular compartmentalisation of copper, iron, manganese, and zinc in the Parkinson's disease brain.

    Science.gov (United States)

    Genoud, Sian; Roberts, Blaine R; Gunn, Adam P; Halliday, Glenda M; Lewis, Simon J G; Ball, Helen J; Hare, Dominic J; Double, Kay L

    2017-10-18

    Elevated iron and decreased copper levels are cardinal features of the degenerating substantia nigra pars compacta in the Parkinson's disease brain. Both of these redox-active metals, and fellow transition metals manganese and zinc, are found at high concentrations within the midbrain and participate in a range of unique biological reactions. We examined the total metal content and cellular compartmentalisation of manganese, iron, copper and zinc in the degenerating substantia nigra, disease-affected but non-degenerating fusiform gyrus, and unaffected occipital cortex in the post mortem Parkinson's disease brain compared with age-matched controls. An expected increase in iron and a decrease in copper concentration was isolated to the soluble cellular fraction, encompassing both interstitial and cytosolic metals and metal-binding proteins, rather than the membrane-associated or insoluble fractions. Manganese and zinc levels did not differ between experimental groups. Altered Fe and Cu levels were unrelated to Braak pathological staging in our cases of late-stage (Braak stage V and VI) disease. The data supports our hypothesis that regional alterations in Fe and Cu, and in proteins that utilise these metals, contribute to the regional selectively of neuronal vulnerability in this disorder.

  20. Iron and copper interact during their uptake and deposition in the brain and other organs of developing rats exposed to dietary excess of the two metals.

    Science.gov (United States)

    Crowe, A; Morgan, E H

    1996-01-01

    This study examined the effect of iron and copper loading on rat brain, liver, kidney, femur, blood and plasma concentrations of these metals and iron transport into the organs during development. Dams were fed control diets or iron-loaded diets (20 g/kg carbonyl iron) with either distilled water or copper-loaded water (350 mg/L) beginning at d 20 of pregnancy. The weanlings also had access to the diets and water supply and were examined at 15, 21 and 63 d of age. The iron content of the liver was 17- to 30-fold greater in iron-loaded rats than in controls, whereas liver, kidney and plasma copper levels generally were lower. Iron loading alone did not increase brain iron concentrations, suggesting the blood-brain barrier is already developed at birth. However, dual loading of iron and copper resulted in elevated concentrations of brain non-heme iron and copper in 15- and 63-d-old rats compared with animals loaded with iron alone. These results suggest that brain iron uptake mechanisms may be different when excess copper is present. Liver non-heme iron was also greater in copper-loaded rats, irrespective of iron status. However, kidney iron concentrations generally were not affected by dietary copper. In rats fed the copper-containing diet, the uptake of iron into brain and liver was significantly lower than in those fed the control diet, suggesting that copper loading can decrease iron uptake into organs. It is concluded that combined dietary supplementation with iron and copper can alter the metabolism of each metal. These changes are age and organ dependent. Developing rats may be very susceptible to these combined overload states because significant effects are seen in early adulthood.

  1. Effects of chloride, sulfate and natural organic matter (NOM) on the accumulation and release of trace-level inorganic contaminants from corroding iron.

    Science.gov (United States)

    Peng, Ching-Yu; Ferguson, John F; Korshin, Gregory V

    2013-09-15

    This study examined effects of varying levels of anions (chloride and sulfate) and natural organic matter (NOM) on iron release from and accumulation of inorganic contaminants in corrosion scales formed on iron coupons exposed to drinking water. Changes of concentrations of sulfate and chloride were observed to affect iron release and, in lesser extent, the retention of representative inorganic contaminants (vanadium, chromium, nickel, copper, zinc, arsenic, cadmium, lead and uranium); but, effects of NOM were more pronounced. DOC concentration of 1 mg/L caused iron release to increase, with average soluble and total iron concentrations being four and two times, respectively, higher than those in the absence of NOM. In the presence of NOM, the retention of inorganic contaminants by corrosion scales was reduced. This was especially prominent for lead, vanadium, chromium and copper whose retention by the scales decreased from >80% in the absence of NOM to NOM and chloride levels. Modeling indicated that the observed effects were associated with the formation of metal-NOM complexes and effects of NOM on the sorption of the inorganic contaminants on solid phases that are typical for iron corrosion in drinking water. Copyright © 2013 Elsevier Ltd. All rights reserved.

  2. Effect of Nano Iron and Solupotasse Fertilizers on Accumulation of Nutrient Elements and Quality of Two Onion (Allium cepa Cultivars

    Directory of Open Access Journals (Sweden)

    Ali Joghatay

    2015-11-01

    Full Text Available To study the effect of nano iron and solupotass on agronomic and physiological traits of two onion cultivars, a factorial experiment was conducted in complete randomized block design with 32 treatments and three replications in Joghatai of Khorasan-e- Razavi province, Iran. Treatments consisted of two onion cultivars (red, yellow and four levels (0, 1, 2, 3 kg per hectare of nano iron chelat and four levels of solupotass (0, 5, 10, 15 kg per hectare. Results showed that the effect of nano iron and solupotasse on fresh weight, dry weight, pyrovic acid and macro element (N, P, S contents were significant at %1 levels. Application nano iron, solupotasse to red onion cultivar increased dry weight significantly at the %5 level. Highest onion weight was obtained by using 2 kg nano iron and 15 kg solupotasse (17.3 g. Use of nano iron and solupotasse highly increased the pyruvic acid percentage (1.07 mM. Highest rate of pyruvic acid obtained by application of 3 and 15 kg nano iron and solupotasse respectively. Application of nano iron on the sulfur and nitrogen contents of onion were significant. Use of 2 kg/ha of nano iron exhibited highest increase in these elements. Thus, soil application of 10 kg/ha solupotasse, 3 kg/ha nano iron would highly increase red onion traits mentioned above.

  3. Quantitative Susceptibility Mapping Reveals an Association between Brain Iron Load and Depression Severity

    Directory of Open Access Journals (Sweden)

    Shun Yao

    2017-08-01

    Full Text Available Previous studies have detected abnormal serum ferritin levels in patients with depression; however, the results have been inconsistent. This study used quantitative susceptibility mapping (QSM for the first time to examine brain iron concentration in depressed patients and evaluated whether it is related to severity. We included three groups of age- and gender-matched participants: 30 patients with mild-moderate depression (MD, 14 patients with major depression disorder (MDD and 20 control subjects. All participants underwent MR scans with a 3D gradient-echo sequence reconstructing for QSM and performed the 17-item Hamilton Depression Rating Scale (HDRS test. In MDD, the susceptibility value in the bilateral putamen was significantly increased compared with MD or control subjects. In addition, a significant difference was also observed in the left thalamus in MDD patients compared with controls. However, the susceptibility values did not differ between MD patients and controls. The susceptibility values positively correlated with the severity of depression as indicated by the HDRS scores. Our results provide evidence that brain iron deposition may be associated with depression and may even be a biomarker for investigating the pathophysiological mechanism of depression.

  4. Tracking Iron in Multiple Sclerosis: A Combined Imaging and Histopathological Study at 7 Tesla

    Science.gov (United States)

    Bagnato, Francesca; Hametner, Simon; Yao, Bing; van Gelderen, Peter; Merkle, Hellmut; Cantor, Fredric K.; Lassmann, Hans; Duyn, Jeff H.

    2011-01-01

    Previous authors have shown that the transverse relaxivity R[subscript 2][superscript *] and frequency shifts that characterize gradient echo signal decay in magnetic resonance imaging are closely associated with the distribution of iron and myelin in the brain's white matter. In multiple sclerosis, iron accumulation in brain tissue may reflect a…

  5. Age-associated changes of brain copper, iron, and zinc in Alzheimer's disease and dementia with Lewy bodies.

    Science.gov (United States)

    Graham, Stewart F; Nasaruddin, Muhammad Bin; Carey, Manus; Holscher, Christian; McGuinness, Bernadette; Kehoe, Patrick G; Love, Seth; Passmore, Peter; Elliott, Christopher T; Meharg, Andrew A; Green, Brian D

    2014-01-01

    Disease-, age-, and gender-associated changes in brain copper, iron, and zinc were assessed in postmortem neocortical tissue (Brodmann area 7) from patients with moderate Alzheimer's disease (AD) (n = 14), severe AD (n = 28), dementia with Lewy bodies (n = 15), and normal age-matched control subjects (n = 26). Copper was lower (20%; p copper and iron, suggesting gradual age-associated decline of these metals in healthy non-cognitively impaired individuals. Zinc was unaffected in any disease pathologies and no age-associated changes were apparent. Age-associated changes in brain elements warrant further investigation.

  6. Lipocalin-2 enhances angiogenesis in rat brain endothelial cells via reactive oxygen species and iron-dependent mechanisms.

    Science.gov (United States)

    Wu, Limin; Du, Yang; Lok, Josephine; Lo, Eng H; Xing, Changhong

    2015-03-01

    Inflammation is a key part of central nervous system pathophysiology. However, inflammatory factors are now thought to have both beneficial and deleterious effects. Here, we examine the hypothesis that lipocalin-2 (LCN2), an inflammatory molecule that can be up-regulated in the distressed central nervous system, may enhance angiogenesis in brain endothelial cells. Adding LCN2 (0.5-2.0 μg/mL) to RBE (Rat brain endothelial cells). 4 rat brain endothelial cells significantly increased matrigel tube formation and scratch migration, and also elevated levels of iron and reactive oxygen species. Co-treatment with a radical scavenger (U83836E), a Nox inhibitor (apocynin) and an iron chelating agent (deferiprone) significantly dampened the ability of LCN2 to enhance tube formation and scratch migration in brain endothelial cells. These findings provide in vitro proof of the concept that LCN2 can promote angiogenesis via iron- and reactive oxygen species-related pathways, and support the idea that LCN2 may contribute to the neurovascular recovery aspects of inflammation. Angiogenesis is an important part of stroke recovery. In the present study, we examined the hypothesis that lipocalin-2 (LCN2) may enhance angiogenesis in brain endothelial cells. LCN2 promoted tube formation and migration via iron and ROS-related pathways in rat brain endothelial cells. ROS scavengers, Nox inhibitors and iron chelators all dampened the ability of LCN2 to enhance in vitro angiogenesis. These findings support the idea that LCN2 that is released by damaged neurons may act as a 'help me' signal that promotes neurovascular recovery after stroke and brain injury. © 2014 International Society for Neurochemistry.

  7. Sulfur and iron accumulation in three marine-archaeological shipwrecks in the Baltic Sea: The Ghost, the Crown and the Sword

    Science.gov (United States)

    Fors, Yvonne; Grudd, Håkan; Rindby, Anders; Jalilehvand, Farideh; Sandström, Magnus; Cato, Ingemar; Bornmalm, Lennart

    2014-02-01

    Sulfur and iron concentrations in wood from three 17th century shipwrecks in the Baltic Sea, the Ghost wreck, the Crown and the Sword, were obtained by X-ray fluorescence (XRF) scanning. In near anaerobic environments symbiotic microorganisms degrade waterlogged wood, reduce sulfate and promote accumulation of low-valent sulfur compounds, as previously found for the famous wrecks of the Vasa and Mary Rose. Sulfur K-edge X-ray absorption near-edge structure (XANES) analyses of Ghost wreck wood show that organic thiols and disulfides dominate, together with elemental sulfur probably generated by sulfur-oxidizing Beggiatoa bacteria. Iron sulfides were not detected, consistent with the relatively low iron concentration in the wood. In a museum climate with high atmospheric humidity oxidation processes, especially of iron sulfides formed in the presence of corroding iron, may induce post-conservation wood degradation. Subject to more general confirmation by further analyses no severe conservation concerns are expected for the Ghost wreck wood.

  8. Sulfur and iron accumulation in three marine-archaeological shipwrecks in the Baltic Sea: The Ghost, the Crown and the Sword

    Science.gov (United States)

    Fors, Yvonne; Grudd, Håkan; Rindby, Anders; Jalilehvand, Farideh; Sandström, Magnus; Cato, Ingemar; Bornmalm, Lennart

    2014-01-01

    Sulfur and iron concentrations in wood from three 17th century shipwrecks in the Baltic Sea, the Ghost wreck, the Crown and the Sword, were obtained by X-ray fluorescence (XRF) scanning. In near anaerobic environments symbiotic microorganisms degrade waterlogged wood, reduce sulfate and promote accumulation of low-valent sulfur compounds, as previously found for the famous wrecks of the Vasa and Mary Rose. Sulfur K-edge X-ray absorption near-edge structure (XANES) analyses of Ghost wreck wood show that organic thiols and disulfides dominate, together with elemental sulfur probably generated by sulfur-oxidizing Beggiatoa bacteria. Iron sulfides were not detected, consistent with the relatively low iron concentration in the wood. In a museum climate with high atmospheric humidity oxidation processes, especially of iron sulfides formed in the presence of corroding iron, may induce post-conservation wood degradation. Subject to more general confirmation by further analyses no severe conservation concerns are expected for the Ghost wreck wood. PMID:24573214

  9. Iron Deposition Is Positively Related to Cognitive Impairment in Patients with Chronic Mild Traumatic Brain Injury: Assessment with Susceptibility Weighted Imaging

    Directory of Open Access Journals (Sweden)

    Liyan Lu

    2015-01-01

    Full Text Available Background. This study aimed to evaluate the usability of SWI in assessment of brain iron to detect cognitive dysfunction in patients with chronic mild traumatic brain injury (mTBI. Methods. 39 patients with mTBI and 37 normal controls were given the Mini-Mental State Examination (MMSE and underwent SWI scanning at least 6 months after injury. Angle radian values were calculated with phase images. The angle radian values were compared between groups using analysis of covariance, and their association with MMSE scores was analyzed using Spearman correlations. Results. Significantly higher angle radian values (p<0.05 were found in the head of the caudate nucleus, the lenticular nucleus, the hippocampus, the thalamus, the right substantia nigra, the red nucleus, and the splenium of the corpus callosum (SCC in the mTBI group, compared to the control group. MMSE scores were negatively correlated with angle radian values in the right substantia nigra (r=-0.685, p<0.001. Conclusions. Patients with chronic mTBI might have abnormally high accumulations of iron, and their MMSE scores are negatively associated with angle radian values in the right substantia nigra, suggesting a role of SWI in the assessment of cognitive impairments of these patients.

  10. Quantitative T2* magnetic resonance imaging for evaluation of iron deposition in the brain of β-thalassemia patients.

    Science.gov (United States)

    Akhlaghpoor, S; Ghahari, A; Morteza, A; Khalilzadeh, O; Shakourirad, A; Alinaghizadeh, M R

    2012-09-01

    Iron overload is a common clinical problem in patients with β-thalassemia major. The purpose of this study was to assess the presence of excess iron in certain areas of the brain (thalamus, midbrain, adenohypophysis and basal ganglia) in patients with β-thalassemia major and evaluate the association with serum ferritin and liver iron content. A cross-sectional study on 53 patients with β-thalassemia major and 40 healthy controls was carried out. All patients and healthy controls underwent magnetic resonance imaging (MRI) examinations of the brain and liver. Multiecho fast gradient echo sequence was used and T2* values were calculated based on the Brompton protocol. Correlations between T2* values in the brain with T2* values in the liver as well as serum ferritin levels were investigated. There were no significant differences between patients and healthy controls with respect to age and sex. Patients had significantly lower T2* values in basal ganglia (striatum), thalamus and adenohypophysis compared to controls while there were no differences in the midbrain (red nucleus). There were no significant correlations between liver T2* values or serum ferritin with T2* values of basal ganglia (striatum), thalamus and adenohypophysis in patients or healthy controls. There were no significant correlations between T2* values of adenohypophysis and thalamus or basal ganglia (striatum) while these variables were significantly correlated in healthy controls. Serum ferritin and liver iron content may not be good indicators of brain iron deposition in patients with β thalassemia major. Nevertheless, the quantitative T2* MRI technique is useful for evaluation of brain iron overload in β thalassemia major patients.

  11. Cellular distribution of ferric iron, ferritin, transferrin and divalent metal transporter 1 (DMT1) in substantia nigra and basal ganglia of normal and β2-microglobulin deficient mouse brain

    DEFF Research Database (Denmark)

    Moos, Torben; Trinder, D.; Morgan, E.H.

    2000-01-01

    beta-2-microglobulin, blood-brain barrier, gene knock out, iron, neurodegenerative disorders, oxidative damage, subthalamic nucleus......beta-2-microglobulin, blood-brain barrier, gene knock out, iron, neurodegenerative disorders, oxidative damage, subthalamic nucleus...

  12. Ammonium accumulation and cell death in a rat 3D brain cell model of glutaric aciduria type I.

    Directory of Open Access Journals (Sweden)

    Paris Jafari

    Full Text Available Glutaric aciduria type I (glutaryl-CoA dehydrogenase deficiency is an inborn error of metabolism that usually manifests in infancy by an acute encephalopathic crisis and often results in permanent motor handicap. Biochemical hallmarks of this disease are elevated levels of glutarate and 3-hydroxyglutarate in blood and urine. The neuropathology of this disease is still poorly understood, as low lysine diet and carnitine supplementation do not always prevent brain damage, even in early-treated patients. We used a 3D in vitro model of rat organotypic brain cell cultures in aggregates to mimic glutaric aciduria type I by repeated administration of 1 mM glutarate or 3-hydroxyglutarate at two time points representing different developmental stages. Both metabolites were deleterious for the developing brain cells, with 3-hydroxyglutarate being the most toxic metabolite in our model. Astrocytes were the cells most strongly affected by metabolite exposure. In culture medium, we observed an up to 11-fold increase of ammonium in the culture medium with a concomitant decrease of glutamine. We further observed an increase in lactate and a concomitant decrease in glucose. Exposure to 3-hydroxyglutarate led to a significantly increased cell death rate. Thus, we propose a three step model for brain damage in glutaric aciduria type I: (i 3-OHGA causes the death of astrocytes, (ii deficiency of the astrocytic enzyme glutamine synthetase leads to intracerebral ammonium accumulation, and (iii high ammonium triggers secondary death of other brain cells. These unexpected findings need to be further investigated and verified in vivo. They suggest that intracerebral ammonium accumulation might be an important target for the development of more effective treatment strategies to prevent brain damage in patients with glutaric aciduria type I.

  13. Parkinson’s Disease: The Mitochondria-Iron Link

    Directory of Open Access Journals (Sweden)

    Yorka Muñoz

    2016-01-01

    Full Text Available Mitochondrial dysfunction, iron accumulation, and oxidative damage are conditions often found in damaged brain areas of Parkinson’s disease. We propose that a causal link exists between these three events. Mitochondrial dysfunction results not only in increased reactive oxygen species production but also in decreased iron-sulfur cluster synthesis and unorthodox activation of Iron Regulatory Protein 1 (IRP1, a key regulator of cell iron homeostasis. In turn, IRP1 activation results in iron accumulation and hydroxyl radical-mediated damage. These three occurrences—mitochondrial dysfunction, iron accumulation, and oxidative damage—generate a positive feedback loop of increased iron accumulation and oxidative stress. Here, we review the evidence that points to a link between mitochondrial dysfunction and iron accumulation as early events in the development of sporadic and genetic cases of Parkinson’s disease. Finally, an attempt is done to contextualize the possible relationship between mitochondria dysfunction and iron dyshomeostasis. Based on published evidence, we propose that iron chelation—by decreasing iron-associated oxidative damage and by inducing cell survival and cell-rescue pathways—is a viable therapy for retarding this cycle.

  14. Relationship between brain accumulation of manganese and aberration of hippocampal adult neurogenesis after oral exposure to manganese chloride in mice.

    Science.gov (United States)

    Kikuchihara, Yoh; Abe, Hajime; Tanaka, Takeshi; Kato, Mizuho; Wang, Liyun; Ikarashi, Yoshiaki; Yoshida, Toshinori; Shibutani, Makoto

    2015-05-04

    We previously found persistent aberration of hippocampal adult neurogenesis, along with brain manganese (Mn) accumulation, in mouse offspring after developmental exposure to 800-ppm dietary Mn. Reduction of parvalbumin (Pvalb)(+) γ-aminobutyric acid (GABA)-ergic interneurons in the hilus of the dentate gyrus along with promoter region hypermethylation are thought to be responsible for this aberrant neurogenesis. The present study was conducted to examine the relationship between the induction of aberrant neurogenesis and brain Mn accumulation after oral Mn exposure as well as the responsible mechanism in young adult animals. We used two groups of mice with 28- or 56-day exposure periods to oral MnCl2·xH2O at 800 ppm as Mn, a dose sufficient to lead to aberrant neurogenesis after developmental exposure. A third group of mice received intravenous injections of Mn at 5-mg/kg body weight once weekly for 28 days. The 28-day oral Mn exposure did not cause aberrations in neurogenesis. In contrast, 56-day oral exposure caused aberrations in neurogenesis suggestive of reductions in type 2b and type 3 progenitor cells and immature granule cells in the dentate subgranular zone. Brain Mn accumulation in 56-day exposed cases, as well as in directly Mn-injected cases occurred in parallel with reduction of Pvalb(+) GABAergic interneurons in the dentate hilus, suggesting that this may be responsible for aberrant neurogenesis. For reduction of Pvalb(+) interneurons, suppression of brain-derived neurotrophic factor-mediated signaling of mature granule cells may occur via suppression of c-Fos-mediated neuronal plasticity due to direct Mn-toxicity rather than promoter region hypermethylation of Pvalb. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  15. Dietary guanidinoacetic acid does not accumulate in the brain of healthy men

    DEFF Research Database (Denmark)

    Ostojic, Sergej M.; Ostojic, Jelena

    2018-01-01

    We conducted a secondary analysis of a previously completed trial to determine the effects of 8-week guanidinoacetic acid (GAA) loading on brain GAA levels in five healthy men. Brain magnetic resonance spectroscopy (1H-MRS) was taken at baseline and post-administration, with spectra additionally ...

  16. Heavy metal accumulation in Pseudevernia furfuracea (L.) Zopf from the Karabük iron-steel factory in Karabük, Turkey.

    Science.gov (United States)

    Cansaran-Duman, Demet; Atakol, Orhan; Atasoy, Ilknur; Kahya, Didem; Aras, Sümer; Beyaztaş, Taylan

    2009-01-01

    Pseudevernia furfuracea (L.) Zopf lichen specimens were collected every 5 km starting from around an iron-steel factory located in the central area of Karabük province, up to Yenice Forest. Zn, Cu, Mn, Fe, Pb, Ni, Cd, Cr contents were analyzed in the samples collected from polluted and unpolluted areas. A Pseudevernia furfuracea (L.) Zopf sample from Yenice Forest was used as a control. The reason for this choise was the abundance of species diversity, and therefore sample collection might cause a very low impact on natural population density. The forest is among the 100 forested areas that must be urgently taken under protection according to WWF (World Wildlife Fund) researches. Results of the current study manifested significant variations among the contents of these elements between stations. As expected, the pollution sources, such as iron-steel factory, roads and railroads, industry, heavy traffic, and waste treatment plants, have major impact on the heavy metal accumulation in P. furfuracea (L.) Zopf, and, in accordance to their location, samples 8 and 10 displayed high element accumulation. Surprisingly, although Yenice Forest is under protection, results of our study showed that the region is becoming polluted by the influence of many pollution sources in the area. The present study also confirms the efficient metal accumulation capacity of lichens.

  17. Decreased mTOR signalling reduces mitochondrial ROS in brain via accumulation of the telomerase protein TERT within mitochondria.

    Science.gov (United States)

    Miwa, Satomi; Czapiewski, Rafal; Wan, Tengfei; Bell, Amy; Hill, Kirsten N; von Zglinicki, Thomas; Saretzki, Gabriele

    2016-10-22

    Telomerase in its canonical function maintains telomeres in dividing cells. In addition, the telomerase protein TERT has non-telomeric functions such as shuttling to mitochondria resulting in a decreased oxidative stress, DNA damage and apoptosis. TERT protein persists in adult neurons and can co-localise to mitochondria under various stress conditions. We show here that TERT expression decreased in mouse brain during aging while release of reactive oxygen species (ROS) from the mitochondrial electron transport chain increased. Dietary restriction (DR) caused accumulation of TERT protein in mouse brain mitochondria correlating to decreased ROS release and improved learning and spatial short-term memory. Decreased mTOR signalling is a mediator of DR. Accordingly, feeding mice with rapamycin increased brain mitochondrial TERT and reduced ROS release. Importantly, the beneficial effects of rapamycin on mitochondrial function were absent in brains and fibroblasts from first generation TERT -/- mice, and when TERT shuttling was inhibited by the Src kinase inhibitor bosutinib. Taken together, our data suggests that the mTOR signalling pathway impinges on the mitochondrial localisation of TERT protein, which might in turn contribute to the protection of the brain by DR or rapamycin against age-associated mitochondrial ROS increase and cognitive decline.

  18. A vacuolar iron transporter in tulip, TgVit1, is responsible for blue coloration in petal cells through iron accumulation.

    Science.gov (United States)

    Momonoi, Kazumi; Yoshida, Kumi; Mano, Shoji; Takahashi, Hideyuki; Nakamori, Chihiro; Shoji, Kazuaki; Nitta, Akira; Nishimura, Mikio

    2009-08-01

    Blue color in flowers is due mainly to anthocyanins, and a considerable part of blue coloration can be attributed to metal-complexed anthocyanins. However, the mechanism of metal ion transport into vacuoles and subsequent flower color development has yet to be fully explored. Previously, we studied the mechanism of blue color development specifically at the bottom of the inner perianth in purple tulip petals of Tulipa gesneriana cv. Murasakizuisho. We found that differences in iron content were associated with the development of blue- and purple-colored cells. Here, we identify a vacuolar iron transporter in T. gesneriana (TgVit1), and characterize the localization and function of this transporter protein in tulip petals. The amino acid sequence of TgVit1 is 85% similar that of the Arabidopsis thaliana vacuolar iron transporter AtVIT1, and also showed similarity to the AtVIT1 homolog in yeast, Ca(2+)-sensitive cross-complementer 1 (CCC1). The gene TgVit1 was expressed exclusively in blue-colored epidermal cells, and protein levels increased with increasing mRNA expression and blue coloration. Transient expression experiments revealed that TgVit1 localizes to the vacuolar membrane, and is responsible for the development of the blue color in purple cells. Expression of TgVit1 in yeast rescued the growth defect of ccc1 mutant cells in the presence of high concentrations of FeSO(4). Our results indicate that TgVit1 plays an essential role in blue coloration as a vacuolar iron transporter in tulip petals. These results suggest a new role for involvement of a vacuolar iron transporter in blue flower color development.

  19. Effects of Sesaminol Feeding on BrainAccumulation in a Senescence-Accelerated Mouse-Prone 8.

    Science.gov (United States)

    Katayama, Shigeru; Sugiyama, Haruka; Kushimoto, Shoko; Uchiyama, Yusuke; Hirano, Masato; Nakamura, Soichiro

    2016-06-22

    Alzheimer's disease (AD) is characterized by the progressive accumulation of extracellular β-amyloid (Aβ) aggregates. Recently, the senescence-accelerated mouse-prone 8 (SAMP8) model was highlighted as a useful model of age-related AD. Therefore, we used the SAMP8 mouse to investigate the preventive effects of sesame lignans on the onset of AD-like pathology. In preliminary in vitro studies, sesaminol showed the greatest inhibitory effect on Aβ oligomerization and fibril formation relative to sesamin, sesamolin, and sesaminol triglucoside. Hence, sesaminol was selected for further evaluation in vivo. In SAMP8 mice, feed-through sesaminol (0.05%, w/w, in standard chow) administered over a 16 week period reduced brainaccumulation and decreased serum 8-hydroxydeoxyguanosine, an indicator of oxidative stress. Furthermore, sesaminol administration increased the gene and protein expression of ADAM10, which is a protease centrally involved in the non-amyloidogenic processing of amyloid precursor protein. Taken together, these data suggest that long-term consumption of sesaminol may inhibit the accumulation of pathogenic Aβ in the brain.

  20. Lutein accumulates in subcellular membranes of brain regions in adult rhesus macaques: Relationship to DHA oxidation products.

    Directory of Open Access Journals (Sweden)

    Emily S Mohn

    Full Text Available Lutein, a carotenoid with anti-oxidant functions, preferentially accumulates in primate brain and is positively related to cognition in humans. Docosahexaenoic acid (DHA, an omega-3 polyunsaturated fatty acid (PUFA, is also beneficial for cognition, but is susceptible to oxidation. The present study characterized the membrane distribution of lutein in brain regions important for different domains of cognitive function and determined whether membrane lutein was associated with brain PUFA oxidation.Adult rhesus monkeys were fed a stock diet (~2 mg/day lutein or ~0.5 μmol/kg body weight/day (n = 9 or the stock diet plus a daily supplement of lutein (~4.5 mg/day or~1 μmol/kg body weight/day and zeaxanthin (~0.5 mg/day or 0.1 μmol/kg body weight/day for 6-12 months (n = 4. Nuclear, myelin, mitochondrial, and neuronal plasma membranes were isolated using a Ficoll density gradient from prefrontal cortex (PFC, cerebellum (CER, striatum (ST, and hippocampus (HC. Carotenoids, PUFAs, and PUFA oxidation products were measured using HPLC, GC, and LC-GC/MS, respectively.All-trans-lutein (ng/mg protein was detected in all regions and membranes and was highly variable among monkeys. Lutein/zeaxanthin supplementation significantly increased total concentrations of lutein in serum, PFC and CER, as well as lutein in mitochondrial membranes and total DHA concentrations in PFC only (P<0.05. In PFC and ST, mitochondrial lutein was inversely related to DHA oxidation products, but not those from arachidonic acid (P <0.05.This study provides novel data on subcellular lutein accumulation and its relationship to DHA oxidation in primate brain. These findings support the hypothesis that lutein may be associated with antioxidant functions in the brain.

  1. Lutein accumulates in subcellular membranes of brain regions in adult rhesus macaques: Relationship to DHA oxidation products.

    Science.gov (United States)

    Mohn, Emily S; Erdman, John W; Kuchan, Matthew J; Neuringer, Martha; Johnson, Elizabeth J

    2017-01-01

    Lutein, a carotenoid with anti-oxidant functions, preferentially accumulates in primate brain and is positively related to cognition in humans. Docosahexaenoic acid (DHA), an omega-3 polyunsaturated fatty acid (PUFA), is also beneficial for cognition, but is susceptible to oxidation. The present study characterized the membrane distribution of lutein in brain regions important for different domains of cognitive function and determined whether membrane lutein was associated with brain PUFA oxidation. Adult rhesus monkeys were fed a stock diet (~2 mg/day lutein or ~0.5 μmol/kg body weight/day) (n = 9) or the stock diet plus a daily supplement of lutein (~4.5 mg/day or~1 μmol/kg body weight/day) and zeaxanthin (~0.5 mg/day or 0.1 μmol/kg body weight/day) for 6-12 months (n = 4). Nuclear, myelin, mitochondrial, and neuronal plasma membranes were isolated using a Ficoll density gradient from prefrontal cortex (PFC), cerebellum (CER), striatum (ST), and hippocampus (HC). Carotenoids, PUFAs, and PUFA oxidation products were measured using HPLC, GC, and LC-GC/MS, respectively. All-trans-lutein (ng/mg protein) was detected in all regions and membranes and was highly variable among monkeys. Lutein/zeaxanthin supplementation significantly increased total concentrations of lutein in serum, PFC and CER, as well as lutein in mitochondrial membranes and total DHA concentrations in PFC only (Plutein was inversely related to DHA oxidation products, but not those from arachidonic acid (P lutein accumulation and its relationship to DHA oxidation in primate brain. These findings support the hypothesis that lutein may be associated with antioxidant functions in the brain.

  2. A reduced cerebral metabolic ratio in exercise reflects metabolism and not accumulation of lactate within the human brain

    DEFF Research Database (Denmark)

    Dalsgaard, Mads K; Quistorff, Bjørn; Danielsen, Else R

    2003-01-01

    During maximal exercise lactate taken up by the human brain contributes to reduce the cerebral metabolic ratio, O(2)/(glucose + 1/2 lactate), but it is not known whether the lactate is metabolized or if it accumulates in a distribution volume. In one experiment the cerebral arterio-venous differe......During maximal exercise lactate taken up by the human brain contributes to reduce the cerebral metabolic ratio, O(2)/(glucose + 1/2 lactate), but it is not known whether the lactate is metabolized or if it accumulates in a distribution volume. In one experiment the cerebral arterio......-venous differences (AV) for O(2), glucose (glc) and lactate (lac) were evaluated in nine healthy subjects at rest and during and after exercise to exhaustion. The cerebrospinal fluid (CSF) was drained through a lumbar puncture immediately after exercise, while control values were obtained from six other healthy...... young subjects. In a second experiment magnetic resonance spectroscopy ((1)H-MRS) was performed after exhaustive exercise to assess lactate levels in the brain (n = 5). Exercise increased the AV(O2) from 3.2 +/- 0.1 at rest to 3.5 +/- 0.2 mM (mean +/-s.e.m.; P

  3. The effects of grafted mesenchymal stem cells labeled with iron oxide or cobalt-zinc-iron nanoparticles on the biological macromolecules of rat brain tissue extracts.

    Science.gov (United States)

    Novotna, Bozena; Herynek, Vit; Rossner, Pavel; Turnovcova, Karolina; Jendelova, Pavla

    2017-01-01

    Rat mesenchymal stem cells (rMSCs) labeled with 1) poly-l-lysine-coated superparamagnetic iron oxide nanoparticles or 2) silica-coated cobalt-zinc-iron nanoparticles were implanted into the left brain hemisphere of rats, to assess their effects on the levels of oxidative damage to biological macromolecules in brain tissue. Controls were implanted with unlabeled rMSCs. Animals were sacrificed 24 hours or 4 weeks after the treatment, and the implantation site along with the surrounding tissue was isolated from the brain. At the same intervals, parallel groups of animals were scanned in vivo by magnetic resonance imaging (MRI). The comet assay with enzymes of excision DNA repair (endonuclease III and formamidopyrimidine-DNA glycosylase) was used to analyze breaks and oxidative damage to DNA in the brain tissue. Oxidative damage to proteins and lipids was determined by measuring the levels of carbonyl groups and 15-F2t-isoprostane (enzyme-linked immunosorbent assay). MRI displayed implants of labeled cells as extensive hypointense areas in the brain tissue. In histological sections, the expression of glial fibrillary acidic protein and CD68 was analyzed to detect astrogliosis and inflammatory response. Both contrast labels caused a similar response in the T2-weighted magnetic resonance (MR) image and the signal was clearly visible within 4 weeks after implantation of rMSCs. No increase of oxidative damage to DNA, lipids, or proteins over the control values was detected in any sample of brain tissue from the treated animals. Also, immunohistochemistry did not indicate any serious tissue impairment around the graft. Both tested types of nanoparticles appear to be prospective and safe labels for tracking the transplanted cells by MR.

  4. Changes in calcium and iron levels in the brains of rats during kainate induced epilepsy

    Energy Technology Data Exchange (ETDEWEB)

    Ren, M.-Q.; Ong, W.-Y.; Makjanic, Jagoda; Watt, Frank E-mail: phywattf@nus.edu.sg

    1999-09-02

    Epilepsy is a recurrent disorder of cerebral function characterised by sudden brief attacks of altered consciousness, motor activity or sensory phenomena, and affects approximately 1% of the population. Kainic acid injection induces neuronal degeneration in rats, is associated with glial hypertrophy and proliferation in the CA3-CA4 fields of hippocampal complex, and is a model for temporal lobe epilepsy. In this study we have applied Nuclear Microscopy to the investigation of the elemental changes within the hippocampus and the cortex areas of the rat brain following kainate injection. Analyses of unstained freeze dried tissue sections taken at 1 day and 1, 2, 3 and 4 weeks following injection were carried out using the Nuclear Microscopy facility at the Research Centre for Nuclear Microscopy, National University of Singapore. Quantitative analysis and elemental mapping indicates that there are significant changes in the calcium levels and distributions in the hippocampus as early as 1 day following injection. Preliminary results indicate a rapid increase in cellular calcium. High levels of calcium can activate calcium dependent proteins and phospholipases. Activation of phospholipase A{sub 2} can be harmful to surrounding neurons through free radical damage. In addition to observed increases in calcium, there was evidence of increases in iron levels. This is consistent with measurements in other degenerative brain disorders, and may signal a late surge in free radical production.

  5. Changes in calcium and iron levels in the brains of rats during kainate induced epilepsy

    Science.gov (United States)

    Ren, Min-Qin; Ong, Wei-Yi; Makjanic, Jagoda; Watt, Frank

    1999-10-01

    Epilepsy is a recurrent disorder of cerebral function characterised by sudden brief attacks of altered consciousness, motor activity or sensory phenomena, and affects approximately 1% of the population. Kainic acid injection induces neuronal degeneration in rats, is associated with glial hypertrophy and proliferation in the CA3-CA4 fields of hippocampal complex, and is a model for temporal lobe epilepsy. In this study we have applied Nuclear Microscopy to the investigation of the elemental changes within the hippocampus and the cortex areas of the rat brain following kainate injection. Analyses of unstained freeze dried tissue sections taken at 1 day and 1, 2, 3 and 4 weeks following injection were carried out using the Nuclear Microscopy facility at the Research Centre for Nuclear Microscopy, National University of Singapore. Quantitative analysis and elemental mapping indicates that there are significant changes in the calcium levels and distributions in the hippocampus as early as 1 day following injection. Preliminary results indicate a rapid increase in cellular calcium. High levels of calcium can activate calcium dependent proteins and phospholipases. Activation of phospholipase A 2 can be harmful to surrounding neurons through free radical damage. In addition to observed increases in calcium, there was evidence of increases in iron levels. This is consistent with measurements in other degenerative brain disorders, and may signal a late surge in free radical production.

  6. Burkholderia phytofirmans Inoculation-Induced Changes on the Shoot Cell Anatomy and Iron Accumulation Reveal Novel Components of Arabidopsis-Endophyte Interaction that Can Benefit Downstream Biomass Deconstruction

    Science.gov (United States)

    Zhao, Shuai; Wei, Hui; Lin, Chien-Yuan; Zeng, Yining; Tucker, Melvin P.; Himmel, Michael E.; Ding, Shi-You

    2016-01-01

    It is known that plant growth promoting bacteria (PGPB) elicit positive effects on plant growth and biomass yield. However, the actual mechanism behind the plant-PGPB interaction is poorly understood, and the literature is scarce regarding the thermochemical pretreatability and enzymatic degradability of biomass derived from PGPB-inoculated plants. Most recent transcriptional analyses of PGPB strain Burkholderia phytofirmans PsJN inoculating potato in literature and Arabidopsis in our present study have revealed the expression of genes for ferritin and the biosynthesis and transport of siderophores (i.e., the molecules with high affinity for iron), respectively. The expression of such genes in the shoots of PsJN-inoculated plants prompted us to propose that PsJN-inoculation can improve the host plant's iron uptake and accumulation, which facilitates the downstream plant biomass pretreatment and conversion to simple sugars. In this study, we employed B. phytofirmans PsJN to inoculate the Arabidopsis thaliana plants, and conducted the first investigation for its effects on the biomass yield, the anatomical organization of stems, the iron accumulation, and the pretreatment and enzymatic hydrolysis of harvested biomass. The results showed that the strain PsJN stimulated plant growth in the earlier period of plant development and enlarged the cell size of stem piths, and it also indeed enhanced the essential metals uptake and accumulation in host plants. Moreover, we found that the PsJN-inoculated plant biomass released more glucose and xylose after hot water pretreatment and subsequent co-saccharification, which provided a novel insight into development of lignocellulosic biofuels from renewable biomass resources. PMID:26858740

  7. Burkholderia phytofirmans inoculation-induced changes on the shoot cell anatomy and iron accumulation reveal novel components of Arabidopsis-endophyte interaction that can benefit downstream biomass deconstruction

    Directory of Open Access Journals (Sweden)

    Shuai eZhao

    2016-01-01

    Full Text Available It is known that plant growth promoting bacteria (PGPB elicit positive effects on plant growth and biomass yield. However, the actual mechanism behind the plant-PGPB interaction is poorly understood, and the literature is scarce regarding the thermochemical pretreatability and enzymatic degradability of biomass derived from PGPB-inoculated plants. Most recent transcriptional analyses of PGPB strain Burkholderia phytofirmans PsJN inoculating potato in literature and Arabidopsis in our present study have revealed the expression of genes for ferritin and the biosynthesis and transport of siderophores (i.e. the molecules with high affinity for iron, respectively. The expression of such genes in the shoots of PsJN-inoculated plants prompted us to propose that PsJN-inoculation can improve the host plant’s iron uptake and accumulation, which facilitates the downstream plant biomass pretreatment and conversion to simple sugars. In this study, we employed B. phytofirmans PsJN to inoculate the Arabidopsis thaliana plants, and conducted the first investigation for its effects on the biomass yield, the anatomical organization of stems, the iron accumulation, and the pretreatment and enzymatic hydrolysis of harvested biomass. The results showed that the strain PsJN stimulated plant growth in the earlier period of plant development and enlarged the cell size of stem piths, and it also indeed enhanced the essential metals uptake and accumulation in host plants. Moreover, we found that the PsJN-inoculated plant biomass released more glucose and xylose after hot water pretreatment and subsequent co-saccharification, which provided a novel insight into development of lignocellulosic biofuels from renewable biomass resources.

  8. The abnormal isoform of the prion protein accumulates in late-endosome-like organelles in scrapie-infected mouse brain.

    Science.gov (United States)

    Arnold, J E; Tipler, C; Laszlo, L; Hope, J; Landon, M; Mayer, R J

    1995-08-01

    The prion encephalopathies are characterized by accumulation in the brain of the abnormal form PrPsc of a normal host gene product PrPc. The mechanism and site of formation of PrPsc from PrPc are currently unknown. In this study, ME7 scrapie-infected mouse brain was used to show, both biochemically and by double-labelled immunogold electron microscopy, that proteinase K-resistant PrPsc is enriched in subcellular structures which contain the cation-independent mannose 6-phosphate receptor, ubiquitin-protein conjugates, beta-glucuronidase, and cathepsin B, termed late endosome-like organelles. The glycosylinositol phospholipid membrane-anchored PrPc will enter such compartment for normal degradation and the organelles may therefore act as chambers for the conversion of PrPc into infectious PrPsc in this murine model of scrapie.

  9. Eltrombopag, a thrombopoietin mimetic, crosses the blood-brain barrier and impairs iron-dependent hippocampal neuron dendrite development.

    Science.gov (United States)

    Bastian, T W; Duck, K A; Michalopoulos, G C; Chen, M J; Liu, Z-J; Connor, J R; Lanier, L M; Sola-Visner, M C; Georgieff, M K

    2017-03-01

    Essentials Potential neurodevelopmental side effects of thrombopoietin mimetics need to be considered. The effects of eltrombopag (ELT) on neuronal iron status and dendrite development were assessed. ELT crosses the blood-brain barrier and causes iron deficiency in developing neurons. ELT blunts dendrite maturation, indicating a need for more safety studies before neonatal use. Background Thrombocytopenia is common in sick neonates. Thrombopoietin mimetics (e.g. eltrombopag [ELT]) might provide an alternative therapy for selected neonates with severe and prolonged thrombocytopenia, and for infants and young children with different varieties of thrombocytopenia. However, ELT chelates intracellular iron, which may adversely affect developing organs with high metabolic requirements. Iron deficiency (ID) is particularly deleterious during brain development, impairing neuronal myelination, dopamine signaling and dendritic maturation and ultimately impairing long-term neurological function (e.g. hippocampal-dependent learning and memory). Objective To determine whether ELT crosses the blood-brain barrier (BBB), causes neuronal ID and impairs hippocampal neuron dendrite maturation. Methods ELT transport across the BBB was assessed using primary bovine brain microvascular endothelial cells. Embryonic mouse primary hippocampal neuron cultures were treated with ELT or deferoxamine (DFO, an iron chelator) from 7 days in vitro (DIV) through 14 DIV and assessed for gene expression and neuronal dendrite complexity. Results ELT crossed the BBB in a time-dependent manner. 2 and 6 μm ELT increased Tfr1 and Slc11a2 (iron-responsive genes involved in neuronal iron uptake) mRNA levels, indicating neuronal ID. 6 μm ELT, but not 2 μm ELT, decreased BdnfVI, Camk2a and Vamp1 mRNA levels, suggesting impaired neuronal development and synaptic function. Dendrite branch number and length were reduced in 6 μm ELT-treated neurons, resulting in blunted dendritic arbor complexity that

  10. Providing male rats deficient in iron and n-3 fatty acids with iron and alpha-linolenic acid alone affects brain serotonin and cognition differently from combined provision.

    Science.gov (United States)

    Baumgartner, Jeannine; Smuts, Cornelius M; Zimmermann, Michael B

    2014-06-13

    We recently showed that a combined deficiency of iron (ID) and n-3 fatty acids (n-3 FAD) in rats disrupts brain monoamine metabolism and produces greater memory deficits than ID or n-3 FAD alone. Providing these double-deficient rats with either iron (Fe) or preformed docosahexaenoic acid (DHA)/eicosapentaenoic acid (EPA) alone affected brain monoamine pathways differently from combined repletion and even exacerbated cognitive deficits associated with double-deficiency. Iron is a co-factor of the enzymes responsible for the conversion of alpha-linolenic acid (ALA) to EPA and DHA, thus, the provision of ALA with Fe might be more effective in restoring brain EPA and DHA and improving cognition in double-deficient rats than ALA alone. In this study we examined whether providing double-deficient rats with ALA and Fe, alone or in combination, can correct deficits in monoamine metabolism and cognition associated with double-deficiency. Using a 2 × 2 design, male rats with concurrent ID and n-3 FAD were fed an Fe + ALA, Fe + n-3 FAD, ID + ALA, or ID + n-3 FAD diet for 5 weeks (postnatal day 56-91). Biochemical measures, and spatial working and reference memory (using the Morris water maze) were compared to age-matched controls. In the hippocampus, we found a significant Fe × ALA interaction on DHA: Compared to the group receiving ALA alone, DHA was significantly higher in the Fe + ALA group. In the brain, we found significant antagonistic Fe × ALA interactions on serotonin concentrations. Provision of ALA alone impaired working memory compared with age-matched controls, while in the reference memory task ALA provided with Fe significantly improved performance. These results indicate that providing either iron or ALA alone to double-deficient rats affects serotonin pathways and cognitive performance differently from combined provision. This may be partly explained by the enhancing effect of Fe on the conversion of ALA to EPA and DHA.

  11. Development and Testing of Iron Based Phantoms as Standards for the Diagnosis of Microbleeds and Oxygen Saturation with Applications in Dementia, Stroke, and Traumatic Brain Injury

    Science.gov (United States)

    2013-10-01

    Edwards , N., Mintz, J., 2007. Brain ferritin iron may influence age- and gender- related risks of neurodegeneration. Neurobiol. Aging 28, 414–423...S.E., Lees, A.J., Jenner , P., Marsden, C.D., 1991. Alterations in the levels of iron, ferritin and other tracemetals in Parkinson’s disease and other

  12. Iron-Responsive Olfactory Uptake of Manganese Improves Motor Function Deficits Associated with Iron Deficiency

    Science.gov (United States)

    Kim, Jonghan; Li, Yuan; Buckett, Peter D.; Böhlke, Mark; Thompson, Khristy J.; Takahashi, Masaya; Maher, Timothy J.; Wessling-Resnick, Marianne

    2012-01-01

    Iron-responsive manganese uptake is increased in iron-deficient rats, suggesting that toxicity related to manganese exposure could be modified by iron status. To explore possible interactions, the distribution of intranasally-instilled manganese in control and iron-deficient rat brain was characterized by quantitative image analysis using T1-weighted magnetic resonance imaging (MRI). Manganese accumulation in the brain of iron-deficient rats was doubled after intranasal administration of MnCl2 for 1- or 3-week. Enhanced manganese level was observed in specific brain regions of iron-deficient rats, including the striatum, hippocampus, and prefrontal cortex. Iron-deficient rats spent reduced time on a standard accelerating rotarod bar before falling and with lower peak speed compared to controls; unexpectedly, these measures of motor function significantly improved in iron-deficient rats intranasally-instilled with MnCl2. Although tissue dopamine concentrations were similar in the striatum, dopamine transporter (DAT) and dopamine receptor D1 (D1R) levels were reduced and dopamine receptor D2 (D2R) levels were increased in manganese-instilled rats, suggesting that manganese-induced changes in post-synaptic dopaminergic signaling contribute to the compensatory effect. Enhanced olfactory manganese uptake during iron deficiency appears to be a programmed “rescue response” with beneficial influence on motor impairment due to low iron status. PMID:22479410

  13. Iron-responsive olfactory uptake of manganese improves motor function deficits associated with iron deficiency.

    Directory of Open Access Journals (Sweden)

    Jonghan Kim

    Full Text Available Iron-responsive manganese uptake is increased in iron-deficient rats, suggesting that toxicity related to manganese exposure could be modified by iron status. To explore possible interactions, the distribution of intranasally-instilled manganese in control and iron-deficient rat brain was characterized by quantitative image analysis using T1-weighted magnetic resonance imaging (MRI. Manganese accumulation in the brain of iron-deficient rats was doubled after intranasal administration of MnCl(2 for 1- or 3-week. Enhanced manganese level was observed in specific brain regions of iron-deficient rats, including the striatum, hippocampus, and prefrontal cortex. Iron-deficient rats spent reduced time on a standard accelerating rotarod bar before falling and with lower peak speed compared to controls; unexpectedly, these measures of motor function significantly improved in iron-deficient rats intranasally-instilled with MnCl(2. Although tissue dopamine concentrations were similar in the striatum, dopamine transporter (DAT and dopamine receptor D(1 (D1R levels were reduced and dopamine receptor D(2 (D2R levels were increased in manganese-instilled rats, suggesting that manganese-induced changes in post-synaptic dopaminergic signaling contribute to the compensatory effect. Enhanced olfactory manganese uptake during iron deficiency appears to be a programmed "rescue response" with beneficial influence on motor impairment due to low iron status.

  14. Increased Pittsburgh Compound-B Accumulation in the Subcortical White Matter of Alzheimer's Disease Brain.

    Science.gov (United States)

    Wakabayashi, Yuichi; Ishii, Kazunari; Hosokawa, Chisa; Hyodo, Tomoko; Kaida, Hayato; Yamada, Minoru; Yagyu, Yukinobu; Tsurusaki, Masakatsu; Kozuka, Takenori; Sugimura, Kazuro; Murakami, Takamichi

    2017-03-13

    Using 11C-Pittsburgh compound B (PiB)-PET and MRI volume data, we investigated whether white matter (WM) PiB uptake in Alzheimer's disease (AD) brain is larger than that of cortical PiB uptake-negative (PiB-negative) brain. Forty-five subjects who underwent both PiB-PET and MRI were included in the study (32 AD patients with cortical PiB-positive and 13 cortical amyloid -negative patients). Individual areas of gray matter (GM) and WM were segmented, then regional GM and WM standard uptake value ratio (SUVR) normalized to cerebellar GM with partial volume effects correction was calculated. Three regional SUVRs except WM in the centrum semiovale in the AD group were significantly larger than those in the PiB-negative groups. Frontal WM SUVR in the AD group vs frontal WM SUVR in the PiB-negative group was 2.57 ± 0.55 vs 1.64 ± 0.22; parietal, 2.50 ± 0.52 vs 1.74 ± 0.22; posterior cingulate, 2.84 ± 0.59 vs 1.73 ± 0.22; and WM in the centrum semiovale, 2.21 ± 0.53 vs 2.42 ± 0.36, respectively. We found that PiB uptake in AD brain is significantly larger than that in PiB-negative brain in the frontal, parietal and posterior cingulate subcortical WM, except in the centrum semiovale.

  15. The effect of probiotic bacteria (Lactobacillus acidophilus and Bifidobacterium lactis) on the accumulation of lead in rat brains.

    Science.gov (United States)

    Zanjani, Saman Yahyavi; Eskandari, Mohammad Reza; Kamali, Koorosh; Mohseni, Mehran

    2017-01-01

    Lead is a toxic metal present in different concentrations in a wide variety of food products. Exposure to lead, even to low levels, causes acute and chronic toxicities. Lead can cross the blood-brain barrier and accumulate in the nervous system. Probiotics are live microorganisms that, when used in adequate amounts, confer a health benefit on the host. Although a recent study demonstrated that the studied bacteria have a protective effect against acute lead toxicity, no research has been found that shows the long-term impact of these bacteria in vivo. The current study surveyed the protective effects of two species of probiotics, Lactobacillus acidophilus LA-5 and Bifidobacterium lactis BB-12, that are most widely used in many functional foods against oral lead exposure (4 weeks) in rat brains. The results revealed that, at the end of the second week of chronic exposure to lead and probiotic bacteria, the lowest level of lead belonged to the Lactobacillus group. At the end of the fourth week, the lowest amount of lead was related to the group receiving both types of probiotics. With the physiological benefits of probiotic consumption, the bacterial solution in this study did not show high efficacy in reducing brain lead concentrations.

  16. Exogenous iron redistribution between brain and spleen after the administration of the {sup 57}Fe{sub 3}O{sub 4} ferrofluid into the ventricle of the brain

    Energy Technology Data Exchange (ETDEWEB)

    Gabbasov, Raul, E-mail: gabbasov_rr@nrcki.ru [National Research Centre “Kurchatov Institute”, Moscow (Russian Federation); Polikarpov, Dmitry [Department of Clinical Medicine, Faculty of Medicine and Health Science, Macquarie University, NSW (Australia); Cherepanov, Valery [National Research Centre “Kurchatov Institute”, Moscow (Russian Federation); Chuev, Michael; Mischenko, Ilya [Institute of Physics and Technology, Russian Academy of Sciences, Moscow (Russian Federation); Loginiva, Nadezhda; Loseva, Elena [Institute of Higher Nervous Activity and Neurophysiology, Russian Academy of Sciences, Moscow (Russian Federation); Nikitin, Maxim [Moscow Institute of Physics and Technology, Dolgoprudny (Russian Federation); Panchenko, Vladislav [National Research Centre “Kurchatov Institute”, Moscow (Russian Federation)

    2017-04-01

    Iron clearance pathways after the injection of {sup 57}Fe{sub 3}O{sub 4}-based dextran-stabilized ferrofluid into the brain ventricles were studied by Mössbauer spectroscopy and histologically. The nanoparticles appeared in spleen tissues within 3 h after transcranial injection. We separated and independently estimated concentrations of iron encapsulated in nanoparticles and iron encapsulated in proteins in the all rat organs. It was found that the dextran coated initial nanoparticles of the ferrofluid disintegrated in the brain into separate superparamagnetic nanoparticles within a week after the injection.The nanoparticles completely exited from the brain in a few weeks. The exogenous iron appeared in the spleen in 3 h after the injection and remained in the spleen for more than month. The appearance of additional component in Mössbauer spectra of spleen samples revealed a fundamental difference in the mechanisms of processing of iron nanoparticles in this organ, which was also confirmed by histological examination.

  17. Tissue Localization of Glycosphingolipid Accumulation in a Gaucher Disease Mouse Brain by LC-ESI-MS/MS and High-Resolution MALDI Imaging Mass Spectrometry.

    Science.gov (United States)

    Jones, E Ellen; Zhang, Wujuan; Zhao, Xueheng; Quiason, Cristine; Dale, Stephanie; Shahidi-Latham, Sheerin; Grabowski, Gregory A; Setchell, Kenneth D R; Drake, Richard R; Sun, Ying

    2017-12-01

    To better understand regional brain glycosphingolipid (GSL) accumulation in Gaucher disease (GD) and its relationship to neuropathology, a feasibility study using mass spectrometry and immunohistochemistry was conducted using brains derived from a GD mouse model (4L/PS/NA) homozygous for a mutant GCase (V394L [4L]) and expressing a prosaposin hypomorphic (PS-NA) transgene. Whole brains from GD and control animals were collected using one hemisphere for MALDI FTICR IMS analysis and the other for quantitation by LC-ESI-MS/MS. MALDI IMS detected several HexCers across the brains. Comparison with the brain hematoxylin and eosin (H&E) revealed differential signal distributions in the midbrain, brain stem, and CB of the GD brain versus the control. Quantitation of serial brain sections with LC-ESI-MS/MS supported the imaging results, finding the overall HexCer levels in the 4L/PS-NA brains to be four times higher than the control. LC-ESI-MS/MS also confirmed that the elevated hexosyl isomers were glucosylceramides rather than galactosylceramides. MALDI imaging also detected differential analyte distributions of lactosylceramide species and gangliosides in the 4L/PS-NA brain, which was validated by LC-ESI-MS/MS. Immunohistochemistry revealed regional inflammation, altered autophagy, and defective protein degradation correlating with regions of GSL accumulation, suggesting that specific GSLs may have distinct neuropathological effects.

  18. Characterization of natural variation for zinc, iron and manganese accumulation and zinc exposure response in Brassica rapa L.

    NARCIS (Netherlands)

    Wu, J.; Schat, H.; Koornneef, M.; Wang, X.; Aarts, M.G.M.

    2007-01-01

    Brassica rapa L. is an important vegetable crop in eastern Asia. The objective of this study was to investigate the genetic variation in leaf Zn, Fe and Mn accumulation, Zn toxicity tolerance and Zn efficiency in B. rapa. In total 188 accessions were screened for their Zn-related characteristics in

  19. The accumulation of brain water-free sodium is associated with ischemic damage independent of the blood pressure in female rats.

    Science.gov (United States)

    Sumiyoshi, Manabu; Kitazato, Keiko T; Yagi, Kenji; Miyamoto, Takeshi; Kurashiki, Yoshitaka; Matsushita, Nobuhisa; Kinouchi, Tomoya; Kuwayama, Kazuyuki; Satomi, Junichiro; Nagahiro, Shinji

    2015-08-07

    Estrogen deficiency worsens ischemic stroke outcomes. In ovariectomized (OVX(+)) rats fed a high-salt diet (HSD), an increase in the body Na(+)/water ratio, which characterizes water-free Na(+) accumulation, was associated with detrimental vascular effects independent of the blood pressure (BP). We hypothesized that an increase in brain water-free Na(+) accumulation is associated with ischemic brain damage in OVX(+)/HSD rats. To test our hypothesis we divided female Wistar rats into 4 groups, OVX(+) and OVX(-) rats fed HSD or a normal diet (ND), and subjected them to transient cerebral ischemia. The brain Na(+)/water ratio was increased even in OVX(+)/ND rats and augmented in OVX(+)/HSD rats. The increase in the brain Na(+)/water ratio was positively correlated with expansion of the cortical infarct volume without affecting the BP. Interestingly, OVX(+) was associated with the decreased expression of ATP1α3, a subtype of the Na(+) efflux pump. HSD increased the expression of brain Na(+) influx-related molecules and the mineralocorticoid receptor (MR). The pretreatment of OVX(+)/HSD rats with the MR antagonist eplerenone reduced brain water-free Na(+) accumulation, up-regulated ATP1α3, down-regulated MR, and reduced the cortical infarct volume. Our findings show that the increase in the brain Na(+)/water ratio elicited by estrogen deficiency or HSD is associated with ischemic brain damage BP-independently, suggesting the importance of regulating the accumulation of brain water-free Na(+). The up-regulation of ATP1α3 and the down-regulation of MR may provide a promising therapeutic strategy to attenuate ischemic brain damage in postmenopausal women. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

  20. Accumulation of natural killer cells in ischemic brain tissues and the chemotactic effect of IP-10.

    Science.gov (United States)

    Zhang, Yao; Gao, Zhongming; Wang, Dandan; Zhang, Tongshuai; Sun, Bo; Mu, Lili; Wang, Jinghua; Liu, Yumei; Kong, Qingfei; Liu, Xijun; Zhang, Yue; Zhang, Haoqiang; He, Jiqing; Li, Hulun; Wang, Guangyou

    2014-04-17

    Stroke is accompanied by a distinguished inflammatory reaction that is initiated by the infiltration of immunocytes, expression of cytokines, and other inflammatory mediators. As natural killer cells (NK cells) are a type of cytotoxic lymphocyte critical to the innate immune system, we investigated the mechanism of NK cells-induced brain injuries after cerebral ischemia and the chemotactic effect of IP-10 simultaneously. NK cells infiltration, interferon-gamma (IFN-γ) and IP-10 expression were detected by immunohistochemistry, immunofluorescence, PCR and flow cytometry in human and C57/BL6 wild type mouse ischemic brain tissues. The ischemia area was detected via 2,3,5-triphenyltetrazolium chloride staining. CXCR3 mean fluorescence intensity of isolated NK cells was measured by flow cytometry. The neuronal injury made by NK cells was examined via apoptosis experiment. The chemotactic of IP-10 was detected by migration and permeability assays. In human ischemic brain tissue, infiltrations of NK cells were observed and reached a peak at 2 to 5 days. In a permanent middle cerebral artery occlusion (pMCAO) model, infiltration of NK cells into the ischemic infarct region reached their highest levels 12 hours after ischemia. IFN-γ-positive NK cells and levels of the chemokine IP-10 were also detected within the ischemic region, from 6 hours up to 4 days after pMCAO was performed, and IFN-γ levels decreased after NK cells depletion in vivo. Co-culture experiments of neural cells with NK cells also showed that neural necrosis was induced via IFN-γ. In parallel experiments with IP-10, the presence of CXCR3 indicates that NK cells were affected by IP-10 via CXCR3, and the effect was dose-dependent. After IP-10 depletion in vivo, NK cells decreased. In migration assays and permeability experiments, disintegration of the blood-brain barrier (BBB) was observed following the addition of NK cells. Moreover, in the presence of IP-10 this injury was aggravated. All findings

  1. Antifibrotic effect of xanthohumol in combination with praziquantel is associated with altered redox status and reduced iron accumulation during liver fluke-associated cholangiocarcinogenesis.

    Science.gov (United States)

    Jamnongkan, Wassana; Thanee, Malinee; Yongvanit, Puangrat; Loilome, Watcharin; Thanan, Raynoo; Kimawaha, Phongsaran; Boonmars, Tidarat; Silakit, Runglawan; Namwat, Nisana; Techasen, Anchalee

    2018-01-01

    Cholangiocarcinoma (CCA) caused by infection of the liver fluke Opisthorchis viverrini , (Ov) is the major public health problem in northeast Thailand. Following Ov infection the subsequent molecular changes can be associated by reactive oxygen species (ROS) induced chronic inflammation, advanced periductal fibrosis, and cholangiocarcinogenesis. Notably, resistance to an activation of cell death in prolonged oxidative stress conditions can occur but some damaged/mutated cells could survive and enable clonal expansion. Our study used a natural product, xanthohumol (XN), which is an anti-oxidant and anti-inflammatory compound, to examine whether it could prevent Ov-associated CCA carcinogenesis. We measured the effect of XN with or without praziquantel (PZ), an anti-helminthic treatment, on DNA damage, redox status change including iron accumulation and periductal fibrosis during CCA genesis induced by administration of Ov and N -dinitrosomethylamine (NDMA) in hamsters. Animals were randomly divided into four groups: group I, Ov infection and NDMA administration (ON); group II, Ov infection and NDMA administration and PZ treatment (ONP); the latter 2 groups were similar to group I and II, but group III received additional XN (XON) and group IV received XN plus PZ (XONP). The results showed that high 8-oxodG (a marker of DNA damage) was observed throughout cholangiocarcinogenesis. Moreover, increased expression of CD44v8-10 (a cell surface in regulation of the ROS defense system), whereas decreased expression of phospho-p38 MAPK (a major ROS target), was found during the progression of the bile duct cell transformation. In addition, high accumulation of iron and expression of transferrin receptor-1 (TfR-1) in both malignant bile ducts and inflammatory cells were detected. Furthermore, fibrosis also increased with the highest level being on day 180. On the other hand, the groups of XN with or without PZ supplementations showed an effective reduction in all the markers

  2. Antifibrotic effect of xanthohumol in combination with praziquantel is associated with altered redox status and reduced iron accumulation during liver fluke-associated cholangiocarcinogenesis

    Directory of Open Access Journals (Sweden)

    Wassana Jamnongkan

    2018-01-01

    Full Text Available Cholangiocarcinoma (CCA caused by infection of the liver fluke Opisthorchis viverrini, (Ov is the major public health problem in northeast Thailand. Following Ov infection the subsequent molecular changes can be associated by reactive oxygen species (ROS induced chronic inflammation, advanced periductal fibrosis, and cholangiocarcinogenesis. Notably, resistance to an activation of cell death in prolonged oxidative stress conditions can occur but some damaged/mutated cells could survive and enable clonal expansion. Our study used a natural product, xanthohumol (XN, which is an anti-oxidant and anti-inflammatory compound, to examine whether it could prevent Ov-associated CCA carcinogenesis. We measured the effect of XN with or without praziquantel (PZ, an anti-helminthic treatment, on DNA damage, redox status change including iron accumulation and periductal fibrosis during CCA genesis induced by administration of Ov and N-dinitrosomethylamine (NDMA in hamsters. Animals were randomly divided into four groups: group I, Ov infection and NDMA administration (ON; group II, Ov infection and NDMA administration and PZ treatment (ONP; the latter 2 groups were similar to group I and II, but group III received additional XN (XON and group IV received XN plus PZ (XONP. The results showed that high 8-oxodG (a marker of DNA damage was observed throughout cholangiocarcinogenesis. Moreover, increased expression of CD44v8-10 (a cell surface in regulation of the ROS defense system, whereas decreased expression of phospho-p38MAPK (a major ROS target, was found during the progression of the bile duct cell transformation. In addition, high accumulation of iron and expression of transferrin receptor-1 (TfR-1 in both malignant bile ducts and inflammatory cells were detected. Furthermore, fibrosis also increased with the highest level being on day 180. On the other hand, the groups of XN with or without PZ supplementations showed an effective reduction in all the

  3. Impact of high iron intake on cognition and neurodegeneration in humans and in animal models: a systematic review.

    Science.gov (United States)

    Agrawal, Sonal; Berggren, Kiersten L; Marks, Eileen; Fox, Jonathan H

    2017-06-01

    Accumulation of brain iron is linked to aging and protein-misfolding neurodegenerative diseases. High iron intake may influence important brain health outcomes in later life. The aim of this systematic review was to examine evidence from animal and human studies of the effects of high iron intake or peripheral iron status on adult cognition, brain aging, and neurodegeneration. MEDLINE, Scopus, CAB Abstracts, the Cochrane Central Register of Clinical Trials, and OpenGrey databases were searched. Studies investigating the effect of elevated iron intake at all postnatal life stages in mammalian models and humans on measures of adult brain health were included. Data were extracted and evaluated by two authors independently, with discrepancies resolved by discussion. Neurodegenerative disease diagnosis and/or behavioral/cognitive, biochemical, and brain morphologic findings were used to study the effects of iron intake or peripheral iron status on brain health. Risk of bias was assessed for animal and human studies. PRISMA guidelines for reporting systematic reviews were followed. Thirty-four preclinical and 14 clinical studies were identified from database searches. Thirty-three preclinical studies provided evidence supporting an adverse effect of nutritionally relevant high iron intake in neonates on brain-health-related outcomes in adults. Human studies varied considerably in design, quality, and findings; none investigated the effects of high iron intake in neonates/infants. Human studies are needed to verify whether dietary iron intake levels used in neonates/infants to prevent iron deficiency have effects on brain aging and neurodegenerative disease outcomes.

  4. Transient modulation of acetylcholinesterase activity caused by exposure to dextran-coated iron oxide nanoparticles in brain of adult zebrafish.

    Science.gov (United States)

    de Oliveira, Giovanna Medeiros Tavares; Kist, Luiza Wilges; Pereira, Talita Carneiro Brandão; Bortolotto, Josiane Woutheres; Paquete, Francisco Lima; de Oliveira, Elisa Magno Nunes; Leite, Carlos Eduardo; Bonan, Carla Denise; de Souza Basso, Nara Regina; Papaleo, Ricardo Meurer; Bogo, Maurício Reis

    2014-05-01

    Superparamagnetic iron oxide nanoparticles (SPIONs) are of great interest in nanomedicine due to their capability to act simultaneously as a contrast agent and as a targeted drug delivery system. At present, one of the biggest concerns about the use of SPIONs remains around its toxicity and, for this reason, it is important to establish the safe upper limit for each use. In the present study, SPION coated with cross-linked aminated dextran (CLIO-NH₂) were synthesized and their toxicity to zebrafish brain was investigated. We have evaluated the effect of different CLIO-NH₂ doses (20, 50, 100, 140 and 200 mg/kg) as a function of time after exposure (one, 16, 24 and 48 h) on AChE activity and ache expression in zebrafish brain. The animals exposed to 200 mg/kg and tested 24 h after administration of the nanoparticles have shown decreased AChE activity, reduction in the exploratory performance, significantly higher level of ferric iron in the brains and induction of casp8, casp 9 and jun genes. Taken together, these findings suggest acute brain toxicity by the inhibition of acetylcholinesterase and induction of apoptosis. Copyright © 2014 Elsevier Inc. All rights reserved.

  5. The pattern of amyloid accumulation in the brains of adults with Down syndrome

    Science.gov (United States)

    Annus, Tiina; Wilson, Liam R.; Hong, Young T.; Acosta–Cabronero, Julio; Fryer, Tim D.; Cardenas–Blanco, Arturo; Smith, Robert; Boros, Istvan; Coles, Jonathan P.; Aigbirhio, Franklin I.; Menon, David K.; Zaman, Shahid H.; Nestor, Peter J.; Holland, Anthony J.

    2016-01-01

    Introduction Adults with Down syndrome (DS) invariably develop Alzheimer's disease (AD) neuropathology. Understanding amyloid deposition in DS can yield crucial information about disease pathogenesis. Methods Forty-nine adults with DS aged 25–65 underwent positron emission tomography with Pittsburgh compound–B (PIB). Regional PIB binding was assessed with respect to age, clinical, and cognitive status. Results Abnormal PIB binding became evident from 39 years, first in striatum followed by rostral prefrontal-cingulo-parietal regions, then caudal frontal, rostral temporal, primary sensorimotor and occipital, and finally parahippocampal cortex, thalamus, and amygdala. PIB binding was related to age, diagnostic status, and cognitive function. Discussion PIB binding in DS, first appearing in striatum, began around age 40 and was strongly associated with dementia and cognitive decline. The absence of a substantial time lag between amyloid accumulation and cognitive decline contrasts to sporadic/familial AD and suggests this population's suitability for an amyloid primary prevention trial. PMID:26362596

  6. Evidence for low molecular weight, non-transferrin-bound iron in rat brain and cerebrospinal fluid

    DEFF Research Database (Denmark)

    Moos, Torben; Morgan, Evan H.

    1998-01-01

    Neuroscience, blood-brain barrier, choroid plexus, interstitial fluid, transferrin receptor, uptake......Neuroscience, blood-brain barrier, choroid plexus, interstitial fluid, transferrin receptor, uptake...

  7. Methodological aspects of MRI of transplanted superparamagnetic iron oxide-labeled mesenchymal stem cells in live rat brain.

    Directory of Open Access Journals (Sweden)

    Daria Namestnikova

    Full Text Available In vivo tracking of transplanted mesenchymal stem cells (MSCs migration and homing is vital for understanding the mechanisms of beneficial effects of MSCs transplantation in animal models of diseases and in clinical trials. Transplanted cells can be labeled with superparamagnetic iron oxide (SPIO particles and visualized in vivo using a number of iron sensitive MRI techniques. However, the applicability of those techniques for SPIO-labeled MSCs tracking in live brain has not been sufficiently investigated. The goal of this study was to estimate the efficiency of various MRI techniques of SPIO-labeled cell tracing in the brain. To achieve that goal, the precision and specificity of T2WI, T2*WI and SWI (Susceptibility-Weighted Imaging techniques of SPIO-labeled MSCs tracing in vitro and in live rat brain were for the first time compared in the same experiment. We have shown that SWI presents the most sensitive pulse sequence for SPIO-labeled MSCs MR visualization. After intracerebral administration due to limitations caused by local micro-hemorrhages the visualization threshold was 102 cells, while after intra-arterial transplantation SWI permitted detection of several cells or even single cells. There is just one publication claiming detection of individual SPIO-labeled MSCs in live brain, while the other state much lower sensitivity, describe detection of different cell types or high resolution tracing of MSCs in other tissues. This study confirms the possibility of single cell tracing in live brain and outlines the necessary conditions. SWI is a method convenient for the detection of single SPIO labeled MSCs and small groups of SPIO labeled MSCs in brain tissue and can be appropriate for monitoring migration and homing of transplanted cells in basic and translational neuroscience.

  8. Methodological aspects of MRI of transplanted superparamagnetic iron oxide-labeled mesenchymal stem cells in live rat brain.

    Science.gov (United States)

    Namestnikova, Daria; Gubskiy, Ilya; Kholodenko, Irina; Melnikov, Pavel; Sukhinich, Kirill; Gabashvili, Anna; Vishnevskiy, Daniil; Soloveva, Anastasia; Abakumov, Maxim; Vakhrushev, Igor; Lupatov, Alexei; Chekhonin, Vladimir; Gubsky, Leonid; Yarygin, Konstantin

    2017-01-01

    In vivo tracking of transplanted mesenchymal stem cells (MSCs) migration and homing is vital for understanding the mechanisms of beneficial effects of MSCs transplantation in animal models of diseases and in clinical trials. Transplanted cells can be labeled with superparamagnetic iron oxide (SPIO) particles and visualized in vivo using a number of iron sensitive MRI techniques. However, the applicability of those techniques for SPIO-labeled MSCs tracking in live brain has not been sufficiently investigated. The goal of this study was to estimate the efficiency of various MRI techniques of SPIO-labeled cell tracing in the brain. To achieve that goal, the precision and specificity of T2WI, T2*WI and SWI (Susceptibility-Weighted Imaging) techniques of SPIO-labeled MSCs tracing in vitro and in live rat brain were for the first time compared in the same experiment. We have shown that SWI presents the most sensitive pulse sequence for SPIO-labeled MSCs MR visualization. After intracerebral administration due to limitations caused by local micro-hemorrhages the visualization threshold was 102 cells, while after intra-arterial transplantation SWI permitted detection of several cells or even single cells. There is just one publication claiming detection of individual SPIO-labeled MSCs in live brain, while the other state much lower sensitivity, describe detection of different cell types or high resolution tracing of MSCs in other tissues. This study confirms the possibility of single cell tracing in live brain and outlines the necessary conditions. SWI is a method convenient for the detection of single SPIO labeled MSCs and small groups of SPIO labeled MSCs in brain tissue and can be appropriate for monitoring migration and homing of transplanted cells in basic and translational neuroscience.

  9. Inflammation-induced brain endothelial activation leads to uptake of electrostatically stabilized iron oxide nanoparticles via sulfated glycosaminoglycans.

    Science.gov (United States)

    Berndt, Dominique; Millward, Jason M; Schnorr, Jörg; Taupitz, Matthias; Stangl, Verena; Paul, Friedemann; Wagner, Susanne; Wuerfel, Jens T; Sack, Ingolf; Ludwig, Antje; Infante-Duarte, Carmen

    2017-05-01

    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.3 cells, which we confirmed in primary endothelial cells and in bEnd.3 cells cultured under shear stress. Transmission electron microscopy and blocking experiments revealed that during inflammation VSOP were endocytosed by bEnd.3. Modified sulfated glycosaminoglycans (GAG) on inflamed brain endothelial cells were the primary binding site for VSOP, as GAG degradation and inhibition of GAG sulfation reduced VSOP uptake. Thus, VSOP-based MRI is sensitive to visualize early neuroinflammatory processes such as GAG modifications on brain endothelial cells. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. The oxidation states and chemical environments of iron and zinc as potential indicators of brain tumour malignancy grade - preliminary results.

    Science.gov (United States)

    Wandzilak, Aleksandra; Czyzycki, Mateusz; Wrobel, Pawel; Szczerbowska-Boruchowska, Magdalena; Radwanska, Edyta; Adamek, Dariusz; Lankosz, Marek

    2013-11-01

    Despite the enormous advances in medicine, brain tumours are still among the lesser-known types of tumours and carry the worst prognoses. Transition metals are believed to play an essential role in carcinogenesis. The aim of this study was to determine differences in the average oxidation state and trends in the changes in the chemical environment of iron and zinc contained in healthy and neoplastic tissues of the human brain. For this purpose, X-ray Absorption Spectroscopy was used, which enables the study of disordered matter. The samples were taken intraoperatively and then immediately frozen to slow down chemical processes. Sixteen tumour samples with various malignancy grades were studied as well as one control sample. For each sample four to eight spectra were recorded, with a shift between them not greater than 0.2 eV. In all of the samples, iron occurred in compounds with both Fe(2+) and Fe(3+). However, the ratio of Fe(ii) to Fe(iii) content in the tissue visibly increased with the tumour malignancy grade. The change in the oxidation state of iron did not correlate with the hypoxia level of the tissues. Analysis of EXAFS spectra of zinc atoms showed that the chemical environment of zinc atoms differed with the tumour malignancy grade. Additionally, cryogenic conditions were found to produce positive results in studies of biological samples, whose form under such conditions is close to their native state, without preparation-caused artefacts.

  11. Tregs Modulate Lymphocyte Proliferation, Activation, and Resident-Memory T-Cell Accumulation within the Brain during MCMV Infection.

    Directory of Open Access Journals (Sweden)

    Sujata Prasad

    Full Text Available Accumulation and retention of regulatory T-cells (Tregs has been reported within post viral-encephalitic brains, however, the full extent to which these cells modulate neuroinflammation is yet to be elucidated. Here, we used Foxp3-DTR (diphtheria toxin receptor knock-in transgenic mice, which upon administration of low dose diphtheria toxin (DTx results in specific deletion of Tregs. We investigated the proliferation status of various immune cell subtypes within inflamed central nervous system (CNS tissue. Depletion of Tregs resulted in increased proliferation of both CD8+ and CD4+ T-cell subsets within the brain at 14 d post infection (dpi when compared to Treg-sufficient animals. At 30 dpi, while proliferation of CD8+ T-cells was controlled within brains of both Treg-depleted and undepleted mice, proliferation of CD4+ T-cells remained significantly enhanced with DTx-treatment. Previous studies have demonstrated that Treg numbers within the brain rebound following DTx treatment to even higher numbers than in untreated animals. Despite this rebound, CD8+ and CD4+ T-cells proliferated at a higher rate when compared to that of Treg-sufficient mice, thus maintaining sustained neuroinflammation. Furthermore, at 30 dpi we found the majority of CD8+ T-cells were CD127hi KLRG1- indicating that the cells were long lived memory precursor cells. These cells showed marked elevation of CD103 expression, a marker of tissue resident-memory T-cells (TRM in the CNS, in untreated animals when compared to DTx-treated animals suggesting that generation of TRM is impaired upon Treg depletion. Moreover, the effector function of TRM as indicated by granzyme B production in response to peptide re-stimulation was found to be more potent in Treg-sufficient animals. Taken together, our findings demonstrate that Tregs limit neuroinflammatory responses to viral infection by controlling cell proliferation and may direct a larger proportion of lymphocytes within the brain to

  12. Paired Helical Filaments from Alzheimer Disease Brain Induce Intracellular Accumulation of Tau Protein in Aggresomes*

    Science.gov (United States)

    Santa-Maria, Ismael; Varghese, Merina; Ksiȩżak-Reding, Hanna; Dzhun, Anastasiya; Wang, Jun; Pasinetti, Giulio M.

    2012-01-01

    Abnormal folding of tau protein leads to the generation of paired helical filaments (PHFs) and neurofibrillary tangles, a key neuropathological feature in Alzheimer disease and tauopathies. A specific anatomical pattern of pathological changes developing in the brain suggests that once tau pathology is initiated it propagates between neighboring neuronal cells, possibly spreading along the axonal network. We studied whether PHFs released from degenerating neurons could be taken up by surrounding cells and promote spreading of tau pathology. Neuronal and non-neuronal cells overexpressing green fluorescent protein-tagged tau (GFP-Tau) were treated with isolated fractions of human Alzheimer disease-derived PHFs for 24 h. We found that cells internalized PHFs through an endocytic mechanism and developed intracellular GFP-Tau aggregates with attributes of aggresomes. This was particularly evident by the perinuclear localization of aggregates and redistribution of the vimentin intermediate filament network and retrograde motor protein dynein. Furthermore, the content of Sarkosyl-insoluble tau, a measure of abnormal tau aggregation, increased 3-fold in PHF-treated cells. An exosome-related mechanism did not appear to be involved in the release of GFP-Tau from untreated cells. The evidence that cells can internalize PHFs, leading to formation of aggresome-like bodies, opens new therapeutic avenues to prevent propagation and spreading of tau pathology. PMID:22496370

  13. Mössbauer study of exogenous iron redistribution between the brain and the liver after administration of 57Fe3O4 ferrofluid in the ventricle of the rat brain

    Science.gov (United States)

    Polikarpov, Dmitry; Gabbasov, Raul; Cherepanov, Valery; Loginova, Natalia; Loseva, Elena; Nikitin, Maxim; Yurenia, Anton; Panchenko, Vladislav

    2015-04-01

    Iron clearance pathways after the injection of 57Fe3O4-based ferrofluid into the brain ventricles were studied histologically and by Mössbauer spectroscopy. It was found that the dextran coated initial nanobeads of the ferrofluid disintegrated in the brain into separate superparamagnetic nanoparticles within a week after the injection. The exogenous iron completely exited all ventricular cavities of the brain within a week after the injection but remained in the white matter for months. Kupffer cells with the exogenous iron appeared in the rat liver 2 hours after the injection. Their concentration reached its maximum on the third day and dropped to zero within a week. The exogenous iron appeared in the spleen a week after the injection and remained in the spleen for months.

  14. Mössbauer study of exogenous iron redistribution between the brain and the liver after administration of {sup 57}Fe{sub 3}O{sub 4} ferrofluid in the ventricle of the rat brain

    Energy Technology Data Exchange (ETDEWEB)

    Polikarpov, Dmitry, E-mail: polikarpov.imp@gmail.com [National Research Center “Kurchatov Institute”, Moscow (Russian Federation); Russian National Research Medical University named after N.I.Pirogov, Moscow (Russian Federation); Gabbasov, Raul; Cherepanov, Valery [National Research Center “Kurchatov Institute”, Moscow (Russian Federation); Loginova, Natalia; Loseva, Elena [Institute of Higher Nervous Activity and Neurophysiology, Russian Academy of Sciences, Moscow (Russian Federation); Nikitin, Maxim [Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow (Russian Federation); Yurenia, Anton; Panchenko, Vladislav [National Research Center “Kurchatov Institute”, Moscow (Russian Federation); Lomonosov Moscow State University, Moscow (Russian Federation)

    2015-04-15

    Iron clearance pathways after the injection of {sup 57}Fe{sub 3}O{sub 4}-based ferrofluid into the brain ventricles were studied histologically and by Mössbauer spectroscopy. It was found that the dextran coated initial nanobeads of the ferrofluid disintegrated in the brain into separate superparamagnetic nanoparticles within a week after the injection. The exogenous iron completely exited all ventricular cavities of the brain within a week after the injection but remained in the white matter for months. Kupffer cells with the exogenous iron appeared in the rat liver 2 hours after the injection. Their concentration reached its maximum on the third day and dropped to zero within a week. The exogenous iron appeared in the spleen a week after the injection and remained in the spleen for months.

  15. Accumulation of polybrominated diphenyl ethers in the brain compared with the levels in other tissues among different vertebrates from an e-waste recycling site.

    Science.gov (United States)

    Zhao, Yaxian; Li, Yuanyuan; Qin, Xiaofei; Lou, Qinqin; Qin, Zhanfen

    2016-11-01

    This study aimed to investigate the accumulation of polybrominated diphenyl ethers (PBDEs) in the brain compared with that in other tissues among different vertebrates. We collected mice, chickens, ducks, frogs, and fish from an e-waste recycling region in Taizhou, China, and measured PBDE concentrations in brain, liver and muscle tissues. The levels of PBDE in the tissues of mice, chickens, ducks, frogs and fish ranged 0.45-206, 0.06-18.8, 1.83-112, 2.75-108, and 0.02-32.0 ng/g wet weight, respectively. Preferential distribution in the liver and muscle relative to the brain was observed for PBDEs in mice, chickens, ducks and frogs. However, a high retention in the brain compared to the liver and muscle was observed in fish. Comparison of the brain/liver concentration (B/L) ratios revealed differences in PBDEs accumulation in the brain among these vertebrates. PBDEs accumulation in the brain was greatest in fish, followed by frogs, while the lowest accumulation occurred in the brains of mammals and birds. The findings apparently coincided with the evolution of the blood-brain barrier (BBB) across vertebrates, i.e. the BBB of fish might be less efficient than those of mammals, birds and amphibian. Low brominated congeners (such as BDE-28, BDE-47 and BDE-99) were predominant in the brains of investigated vertebrates, whereas BDE-209 was most abundant in liver and muscle tissues of mice, chickens and ducks. Significant differences in B/L ratios among PBDE congeners were found in both mice and chickens (p < 0.05). Particularly in mice, the B/L ratios of PBDE congeners presented a declining trend with increased bromine number. Our findings suggested that low brominated congeners might have a higher capacity to penetrate the BBB and accumulate in the brain, whereas high brominated congeners such as BDE-209 might have less potency to pass through the barrier. Further experimental studies are needed to confirm our findings. Copyright © 2016 Elsevier Ltd. All rights

  16. Polyethyleneimine-modified iron oxide nanoparticles for brain tumor drug delivery using magnetic targeting and intra-carotid administration

    Science.gov (United States)

    Chertok, Beata; David, Allan E.; Yang, Victor C.

    2010-01-01

    This study aimed to examine the applicability of polyethyleneimine (PEI)-modified magnetic nanoparticles (GPEI) as a potential vascular drug/gene carrier to brain tumors. In vitro, GPEI exhibited high cell association and low cell toxicity – properties which are highly desirable for intracellular drug/gene delivery. In addition, a high saturation magnetization of 93 emu/g Fe was expected to facilitate magnetic targeting of GPEI to brain tumor lesions. However, following intravenous administration, GPEI could not be magnetically accumulated in tumors of rats harboring orthotopic 9L-gliosarcomas due to its poor pharmacokinetic properties, reflected by a negligibly low plasma AUC of 12 ± 3 μg Fe/ml*min. To improve “passive” GPEI presentation to brain tumor vasculature for subsequent “active” magnetic capture, we examined the intra-carotid route as an alternative for nanoparticle administration. Intra-carotid administration in conjunction with magnetic targeting resulted in 30-fold (p = 0.002) increase in tumor entrapment of GPEI compared to that seen with intravenous administration. In addition, magnetic accumulation of cationic GPEI (ζ-potential = + 37.2 mV) in tumor lesions was 5.2-fold higher (p = 0.004) than that achieved with slightly anionic G100 (ζ-potential = −12 mV) following intra-carotid administration, while no significant accumulation difference was detected between the two types of nanoparticles in the contra-lateral brain (p = 0.187). These promising results warrant further investigation of GPEI as a potential cell-permeable, magnetically-responsive platform for brain tumor delivery of drugs and genes. PMID:20494439

  17. Impact of P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2) gene dosage on plasma pharmacokinetics and brain accumulation of dasatinib, sorafenib, and sunitinib.

    NARCIS (Netherlands)

    Tang, S.C.; Vries, N. de; Sparidans, R.W.; Wagenaar, E.; Beijnen, J.H.; Schinkel, A.H.

    2013-01-01

    Low brain accumulation of anticancer drugs due to efflux transporters may limit chemotherapeutic efficacy, necessitating a better understanding of the underlying mechanisms. P-glycoprotein (Abcb1a/1b) and breast cancer resistance protein (Abcg2) combination knockout mice often display

  18. Mapping and characterization of iron compounds in Alzheimer's tissue

    Energy Technology Data Exchange (ETDEWEB)

    Collingwood, Joanna; Dobson, Jon [Keele

    2008-06-16

    Understanding the management of iron in the brain is of great importance in the study of neurodegeneration, where regional iron overload is frequently evident. A variety of approaches have been employed, from quantifying iron in various anatomical structures, to identifying genetic risk factors related to iron metabolism, and exploring chelation approaches to tackle iron overload in neurodegenerative disease. However, the ease with which iron can change valence state ensures that it is present in vivo in a wide variety of forms, both soluble and insoluble. Here, we review recent developments in approaches to locate and identify iron compounds in neurodegenerative tissue. In addition to complementary techniques that allow us to quantify and identify iron compounds using magnetometry, extraction, and electron microscopy, we are utilizing a powerful combined mapping/characterization approach with synchrotron X-rays. This has enabled the location and characterization of iron accumulations containing magnetite and ferritin in human Alzheimer's disease (AD) brain tissue sections in situ at micron-resolution. It is hoped that such approaches will contribute to our understanding of the role of unusual iron accumulations in disease pathogenesis, and optimise the potential to use brain iron as a clinical biomarker for early detection and diagnosis.

  19. Regional distributions of manganese, iron, copper, and zinc in the brains of 6-hydroxydopamine-induced parkinsonian rats.

    Science.gov (United States)

    Tarohda, Tohru; Ishida, Yasushi; Kawai, Keiichi; Yamamoto, Masayoshi; Amano, Ryohei

    2005-09-01

    Time courses of changes in manganese, iron, copper, and zinc concentrations were examined in regions of the brain of a 6-hydroxydopamine (6-OHDA)-induced rat model of Parkinson's disease using inductively coupled plasma mass spectrometry (ICP-MS). The concentrations were simultaneously determined in brain section at the level of the substantia nigra 1, 3, 7, 10, 14, and 21 days after the 6-OHDA treatment and compared with those of control rats. The distributions of these elements were obtained for 18 regions of the sagittal section (1-mm thick). The ICP-MS results indicated that Mn, Fe, Cu, and Zn levels of the 6-OHDA-induced parkinsonian brain were observed to increase in all regions that lay along the dopaminergic pathway. In the substantia nigra, the increase in Mn level occurred rapidly from 3 to 7 days and preceded those in the other elements, reaching a plateau in the 6-OHDA brain. Iron and Zn levels increased gradually until 7 days and then increased rapidly from 7 to 10 days. The increase in the copper level was slightly delayed. In other regions, such as the globus pallidus, putamen, and amygdala, the levels of Mn, Fe, Cu, and Zn increased with time after 6-OHDA treatment, although the time courses of their changes were region-specific. These findings contribute to our understanding of the roles of Mn and Fe in the induction of neurological symptoms and progressive loss of dopaminergic neurons in the development of Parkinson's disease. Manganese may hold the key to disturbing cellular Fe homeostasis and accelerating Fe levels, which play the most important role in the development of Parkinson's disease.

  20. Combined deficiency of iron and (n-3) fatty acids in male rats disrupts brain monoamine metabolism and produces greater memory deficits than iron deficiency or (n-3) fatty acid deficiency alone1-3

    OpenAIRE

    Baumgartner, Jeannine; Smuts, Cornelius M; Malan, Linda; Arnold, Myrtha; Yee, Benjamin K

    2012-01-01

    Deficiencies of iron (Fe) (ID) and (n-3) fatty acids (FA) [(n-3)FAD] may impair brain development and function through shared mechanisms. However, little is known about the potential interactions between these 2 common deficiencies. We studied the effects of ID and (n-3)FAD, alone and in combination, on brain monoamine pathways (by measuring monoamines and related gene expression) and spatial working and reference memory (by Morris water maze testing). Using a 2 × 2 design, male rats were fed...

  1. Effects of Lead+Selenium Interaction on Acetylcholinesterase Activity in Brain and Accumulation of Metal in Tissues of Oreochromis niloticus (L., 1758

    Directory of Open Access Journals (Sweden)

    Gülsemin Şen

    2017-06-01

    Full Text Available The potential accumulation of lead in different tissues of Oreochromis niloticus and the effects of selenium in AChE inhibition caused by lead in brain were investigated. Juvenile O. niloticus samples were exposed to combination of 1 mg L-1 and 2 mg L-1 lead and 1mg L-1 lead+2mg L-1 selenium and 2mg L-1 lead+4mg L-1 selenium for 1, 7 and 15 days respectively. The accumulation of lead in gill, brain, liver and muscle tissues was analyzed by Inductively Coupled Plasma Mass Spectrometry (ICP-MS as well as brain acetylcholinesterase (AChE, E.C.3.1.1.7 enzyme activity was also analyzed by spectrophotometric method. No mortality was observed during lead exposure in relation to time period and exposed concentrations. Lead accumulation was occurred in all tissues in relation to time. Maximum lead accumulation occurred in brain tissue, followed by the liver, gills and muscle tissues in relation to time period. Selenium caused decrease accumulation of lead in tissues (all selenium mixtures in muscle tissue on the first day, 1mg L-1 Pb+2mg L-1 selenium in gill tissue on the seventh day, in liver tissue on the seventh day except 2mg L-1 Pb+4mg L-1 selenium mixtures at the end of each of all three test periods. Inhibition of AChE activity was caused by the highest concentration and by the short-term effect of lead. Such effect of lead was eliminated by selenium mixture. Lead and selenium mixture were resulted an increase in activity on 15th day at the highest concentration. Selenium led to decrease in the accumulation of lead in the tissues and caused to improvement in the loss of AChE activity.

  2. Combined deficiency of iron and (n-3) fatty acids in male rates disrupts brain monoamine metabolism and produces greater memory deficits than iron deficiency or (n-3) fatty acid deficiency alone

    NARCIS (Netherlands)

    Baumgartner, J.; Smuts, C.M.; Malan, L.; Arnold, M.; Yee, B.K.; Bianco, L.E.; Boekschoten, M.V.; Muller, M.R.; Langhans, W.; Hurrell, R.F.; Zimmermann, M.B.

    2012-01-01

    Deficiencies of iron (Fe) (ID) and (n-3) fatty acids (FA) [(n-3)FAD] may impair brain development and function through shared mechanisms. However, little is known about the potential interactions between these 2 common deficiencies. We studied the effects of ID and (n-3)FAD, alone and in

  3. [Iron dysregulation and anemias].

    Science.gov (United States)

    Ikuta, Katsuya

    2015-10-01

    Most iron in the body is utilized as a component of hemoglobin that delivers oxygen to the entire body. Under normal conditions, the iron balance is tightly regulated. However, iron dysregulation does occasionally occur; total iron content reductions cause iron deficiency anemia and overexpression of the iron regulatory peptide hepcidin disturbs iron utilization resulting in anemia of chronic disease. Conversely, the presence of anemia may ultimately lead to iron overload; for example, thalassemia, a common hereditary anemia worldwide, often requires transfusion, but long-term transfusions cause iron accumulation that leads to organ damage and other poor outcomes. On the other hand, there is a possibility that iron overload itself can cause anemia; iron chelation therapy for the post-transfusion iron overload observed in myelodysplastic syndrome or aplastic anemia improves dependency on transfusions in some cases. These observations reflect the extremely close relationship between anemias and iron metabolism.

  4. Excessive Iron and α-Synuclein Oligomer in Brain are Relevant to Pure Apathy in Parkinson Disease.

    Science.gov (United States)

    Wang, Fang; Yu, Shu-Yang; Zuo, Li-Jun; Cao, Chen-Jie; Hu, Yang; Chen, Ze-Jie; Piao, Ying-Shan; Wang, Ya-Jie; Wang, Xiao-Min; Chen, Sheng-Di; Chan, Piu; Zhang, Wei

    2016-07-01

    To investigate the demographic features, clinical features, and potential mechanism in patients with Parkinson disease (PD) with pure apathy. A total of 145 patients with PD without depression and dementia and 30 age-matched controls were consecutively recruited. Patients with PD were evaluated by Apathy Scale (AS), scales for motor symptoms and quality of life. The levels of iron, oxidative and neuroinflammatory factors, α-synuclein oligomer, and dopamine in cerebrospinal fluid (CSF) from patients with PD and controls were detected by enzyme-linked immunosorbent assay, chemical colorimetric method, and high-performance liquid chromatography. Comparisons between PD with pure apathy and with no pure apathy groups and correlation between AS score and the levels of above factors were analyzed. There were 64 (44.14%) cases in PD-apathy group. The PD-apathy group had older age, (97.81 ± 10.82) years versus (61.86 ± 10.80) years, and severer quality of life (P apathy and PD without apathy groups presented no remarkable differences in motor symptoms (P > .05). The levels of iron, hydroxyl radical (·OH), hydrogen peroxide (H2O2), and α-synuclein oligomer in CSF in PD-apathy group were significantly higher than that in PD without the apathy group (P apathy group, iron level was positively correlated with ·OH level (r = .011, P apathy. Patients with PD having pure apathy had older age. Pure apathy reduced quality of life for patients without worsening motor function. Excessive iron and α-synuclein oligomer in brain commonly contributed to pure apathy of PD through potential mechanism of oxidative stress. © The Author(s) 2016.

  5. Mitochondrial Iron-Sulfur Cluster Dysfunction In Neurodegenerative Disease

    Directory of Open Access Journals (Sweden)

    Grazia eIsaya

    2014-03-01

    Full Text Available Growing evidence supports a role for mitochondrial iron metabolism in the pathophysiology of neurodegenerative disorders such as Friedreich ataxia and Parkinson disease as well as in the motor and cognitive decline associated with the aging process. Iron-sulfur enzyme deficits and regional iron accumulation have been observed in each of these conditions. In spite of significant etiological, clinical and pathological differences that exist between Friedreich ataxia and Parkinson disease, it is possible that defects in mitochondrial iron-sulfur clusters biogenesis represent a common underlying mechanism leading to abnormal intracellular iron distribution with mitochondrial iron accumulation, OXPHOS deficits and oxidative stress in susceptible cells and specific regions of the nervous system. Moreover, a similar mechanism may contribute to the age-dependent iron accumulation that occurs in certain brain regions such as the globus pallidus and the substantia nigra. Targeting chelatable iron and reactive oxygen species appear as possible therapeutic options for Friedreich ataxia and Parkinson disease, and possibly other age-related neurodegenerative conditions. However, new technology to interrogate iron-sulfur cluster synthesis in humans is needed to (i assess how defects in this pathway contribute to the natural history of neurodegenerative disorders and (ii develop treatments to correct those defects early in the disease process, before they cause irreversible neuronal cell damage.

  6. In-situ Characterization and Mapping of Iron Compounds in Alzheimer's Tissue

    Energy Technology Data Exchange (ETDEWEB)

    Collingwood, J F; Mikhaylova, A; Davidson, M; Batich, C; Streit, W J; Terry, J; Dobson, J [IIT; (Keele); (Florida)

    2008-06-16

    There is a well-established link between iron overload in the brain and pathology associated with neurodegeneration in a variety of disorders such as Alzheimer's (AD), Parkinson's (PD) and Huntington's (HD) diseases. This association was first discovered in AD by Goodman in 1953, where, in addition to abnormally high concentrations of iron in autopsy brain tissue, iron has also been shown to accumulate at sites of brain pathology such as senile plaques. However, since this discovery, progress in understanding the origin, role and nature of iron compounds associated with neurodegeneration has been slow. Here we report, for the first time, the location and characterization of iron compounds in human AD brain tissue sections. Iron fluorescence was mapped over a frontal-lobe tissue section from an Alzheimer's patient, and anomalous iron concentrations were identified using synchrotron X-ray absorption techniques at 5 {micro}m spatial resolution. Concentrations of ferritin and magnetite, a magnetic iron oxide potentially indicating disrupted brain-iron metabolism, were evident. These results demonstrate a practical means of correlating iron compounds and disease pathology in-situ and have clear implications for disease pathogenesis and potential therapies.

  7. Loss of lysosomal membrane protein NCU-G1 in mice results in spontaneous liver fibrosis with accumulation of lipofuscin and iron in Kupffer cells

    Directory of Open Access Journals (Sweden)

    Xiang Y. Kong

    2014-03-01

    Full Text Available Human kidney predominant protein, NCU-G1, is a highly conserved protein with an unknown biological function. Initially described as a nuclear protein, it was later shown to be a bona fide lysosomal integral membrane protein. To gain insight into the physiological function of NCU-G1, mice with no detectable expression of this gene were created using a gene-trap strategy, and Ncu-g1gt/gt mice were successfully characterized. Lysosomal disorders are mainly caused by lack of or malfunctioning of proteins in the endosomal-lysosomal pathway. The clinical symptoms vary, but often include liver dysfunction. Persistent liver damage activates fibrogenesis and, if unremedied, eventually leads to liver fibrosis/cirrhosis and death. We demonstrate that the disruption of Ncu-g1 results in spontaneous liver fibrosis in mice as the predominant phenotype. Evidence for an increased rate of hepatic cell death, oxidative stress and active fibrogenesis were detected in Ncu-g1gt/gt liver. In addition to collagen deposition, microscopic examination of liver sections revealed accumulation of autofluorescent lipofuscin and iron in Ncu-g1gt/gt Kupffer cells. Because only a few transgenic mouse models have been identified with chronic liver injury and spontaneous liver fibrosis development, we propose that the Ncu-g1gt/gt mouse could be a valuable new tool in the development of novel treatments for the attenuation of fibrosis due to chronic liver damage.

  8. Bio-accumulation of copper, zinc, iron and manganese in oyster Saccostrea cucullata, Snail Cerithium rubus and Clam Tellina angulata from the Bombay coast

    Digital Repository Service at National Institute of Oceanography (India)

    Krishnakumari, L.; Nair, V.R.; Moraes, C.

    and C. rubus. Sexwise, iron content was high in male and manganese in female oysters. In T. angulata male specimens showed maximum zinc content. Stationwise, difference in copper and iron was significant in C. rubus. In general, copper and zinc...

  9. α7 Nicotinic acetylcholine receptor-specific antibody induces inflammation and amyloid β42 accumulation in the mouse brain to impair memory.

    Directory of Open Access Journals (Sweden)

    Olena Lykhmus

    Full Text Available Nicotinic acetylcholine receptors (nAChRs expressed in the brain are involved in regulating cognitive functions, as well as inflammatory reactions. Their density is decreased upon Alzheimer disease accompanied by accumulation of β-amyloid (Aβ42, memory deficit and neuroinflammation. Previously we found that α7 nAChR-specific antibody induced pro-inflammatory interleukin-6 production in U373 glioblastoma cells and that such antibodies were present in the blood of humans. We raised a hypothesis that α7 nAChR-specific antibody can cause neuroinflammation when penetrating the brain. To test this, C57Bl/6 mice were either immunized with extracellular domain of α7 nAChR subunit α7(1-208 or injected with bacterial lipopolysaccharide (LPS for 5 months. We studied their behavior and the presence of α3, α4, α7, β2 and β4 nAChR subunits, Aβ40 and Aβ42 and activated astrocytes in the brain by sandwich ELISA and confocal microscopy. It was found that either LPS injections or immunizations with α7(1-208 resulted in region-specific decrease of α7 and α4β2 and increase of α3β4 nAChRs, accumulation of Aβ42 and activated astrocytes in the brain of mice and worsening of their episodic memory. Intravenously transferred α7 nAChR-specific-antibodies penetrated the brain parenchyma of mice pre-injected with LPS. Our data demonstrate that (1 neuroinflammation is sufficient to provoke the decrease of α7 and α4β2 nAChRs, Aβ42 accumulation and memory impairment in mice and (2 α7(1-208 nAChR-specific antibodies can cause inflammation within the brain resulting in the symptoms typical for Alzheimer disease.

  10. Regional brain amyloid-β accumulation associates with domain-specific cognitive performance in Parkinson disease without dementia.

    Science.gov (United States)

    Akhtar, Rizwan S; Xie, Sharon X; Chen, Yin J; Rick, Jacqueline; Gross, Rachel G; Nasrallah, Ilya M; Van Deerlin, Vivianna M; Trojanowski, John Q; Chen-Plotkin, Alice S; Hurtig, Howard I; Siderowf, Andrew D; Dubroff, Jacob G; Weintraub, Daniel

    2017-01-01

    Parkinson disease patients develop clinically significant cognitive impairment at variable times over their disease course, which is often preceded by milder deficits in memory, visuo-spatial, and executive domains. The significance of amyloid-β accumulation to these problems is unclear. We hypothesized that amyloid-β PET imaging by 18F-florbetapir, a radiotracer that detects fibrillar amyloid-β plaque deposits, would identify subjects with global cognitive impairment or poor performance in individual cognitive domains in non-demented Parkinson disease patients. We assessed 61 non-demented Parkinson disease patients with detailed cognitive assessments and 18F-florbetapir PET brain imaging. Scans were interpreted qualitatively (positive or negative) by two independent nuclear medicine physicians blinded to clinical data, and quantitatively by a novel volume-weighted method. The presence of mild cognitive impairment was determined through an expert consensus process using Level 1 criteria from the Movement Disorder Society. Nineteen participants (31.2%) were diagnosed with mild cognitive impairment and the remainder had normal cognition. Qualitative 18F-florbetapir PET imaging was positive in 15 participants (24.6%). Increasing age and presence of an APOE ε4 allele were associated with higher composite 18F-florbetapir binding. In multivariable models, an abnormal 18F-florbetapir scan by expert rating was not associated with a diagnosis of mild cognitive impairment. However, 18F-florbetapir retention values in the posterior cingulate gyrus inversely correlated with verbal memory performance. Retention values in the frontal cortex, precuneus, and anterior cingulate gyrus retention values inversely correlated with naming performance. Regional cortical amyloid-β amyloid, as measured by 18F-florbetapir PET, may be a biomarker of specific cognitive deficits in non-demented Parkinson disease patients.

  11. [Effects of nano-lead exposure on learning and memory as well as iron homeostasis in brain of offspring rats].

    Science.gov (United States)

    Gao, Jing; Su, Hong; Yin, Jingwen; Cao, Fuyuan; Feng, Peipei; Liu, Nan; Xue, Ling; Zheng, Guoying; Li, Qingzhao; Zhang, Yanshu

    2015-06-01

    To investigate the effects of nano-lead exposure on learning and memory and iron homeostasis in the brain of the offspring rats on postnatal day 21 (PND21) and postnatal day 42 (PND42). Twenty adult pregnant female Sprague-Dawley rats were randomly divided into control group and nano-lead group. Rats in the nano-lead group were orally administrated 10 mg/kg nano-lead, while rats in the control group were administrated an equal volume of normal saline until PND21. On PND21, the offspring rats were weaned and given the same treatment as the pregnant rats until 42 days after birth. The learning and memory ability of offspring rats on PND21 and PND42 was evaluated by Morris water maze test. The hippocampus and cortex s amples of offspring rats on PND21 and PND42 were collected to determine iron and lead levels in the hippocampus and cortex by inductively coupled plasma-mass spectrometry. The distributions of iron in the hippocampus and cortex were observed by Perl's iron staining. The expression levels of ferritin, ferroportin 1 (FPN1), hephaestin (HP), and ceruloplasmin (CP) were measured by enzyme-linked immunosorbent assay. After nano-lead exposure, the iron content in the cortex of offspring rats on PND21 and PND42 in the nano-lead group was significantly higher than those in the control group (32.63 ± 6.03 µg/g vs 27.04 ± 5.82 µg/g, Phippocampus of offspring rats on PND42 in the nano-lead group was significantly higher than that in the control group (56.9 ± 4.37µg/g vs 37.71 ± 6.92µg/g, Phippocampus in the nano-lead group. FPNl level in the cotfex of offspring rats on PND21 in the nano-lead group was significantly lower than that in the control group (3.64 ± 0.23 ng/g vs 4.99 ± 0.95 ng/g, Phippocampus of offspring rats on PND42 in the nano-lead group was significantly lower than that in the control group (2.28 ± 0.51 ng/g vs 3.69 ± 0.69 ng/g, Phippocampus and cortex of offspring rats and affect their learning and memory ability.

  12. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... infancy and childhood can have long-lasting, negative effects on brain health, the American Academy of Pediatrics ... overdose of iron. Iron supplements can cause side effects, such as dark stools, stomach irritation, and heartburn. ...

  13. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... some stages of life, such as pregnancy and childhood, it may be hard to get enough iron ... supports concerns that iron deficiency during infancy and childhood can have long-lasting, negative effects on brain ...

  14. Effect of oral cadmium administration to female rats during pregnancy on zinc, copper, and iron content in placenta, foetal liver, kidney, intestine, and brain

    Energy Technology Data Exchange (ETDEWEB)

    Sowa, B.; Steibert, E.

    1985-02-01

    Cadmium chloride was administered in drinking water at a concentration of 50 ppm cadmium to female rats for 20 days of gestation. The foetuses were then removed from the uteri of the dams. Gestational exposure to oral cadmium resulted in decreased zinc, copper, iron, metallothionein, and thionein-bound zinc content in foetal liver as well as in reduced copper content in placenta and foetal intestine, brain and kidney. Subcellular fractionation of the foetal liver revealed decreased microsomal iron content. Pregnant rats exposed to oral cadmium revealed decreased serum zinc and iron concentration as well as reduced ceruloplasmin activity. The decreased zinc, copper, and iron content in foetal organs is suggested to be causally connected with the diminished availability of these metals in the maternal circulation.

  15. Selective antihypertensive dihydropyridines lower Aβ accumulation by targeting both the production and the clearance of Aβ across the blood-brain barrier.

    Science.gov (United States)

    Paris, Daniel; Bachmeier, Corbin; Patel, Nikunj; Quadros, Amita; Volmar, Claude-Henry; Laporte, Vincent; Ganey, Jim; Beaulieu-Abdelahad, David; Ait-Ghezala, Ghania; Crawford, Fiona; Mullan, Michael J

    2011-01-01

    Several large population-based or clinical trial studies have suggested that certain dihydropyridine (DHP) L-type calcium channel blockers (CCBs) used for the treatment of hypertension may confer protection against the development of Alzheimer disease (AD). However, other studies with drugs of the same class have shown no beneficial clinical effects. To determine whether certain DHPs are able to impact underlying disease processes in AD (specifically the accumulation of the Alzheimer Aβ peptide), we investigated the effect of several antihypertensive DHPs and non-DHP CCBs on Aβ production. Among the antihypertensive DHPs tested, a few, including nilvadipine, nitrendipine and amlodipine inhibited Aβ production in vitro, whereas others had no effect or raised Aβ levels. In vivo, nilvadipine and nitrendipine acutely reduced brain Aβ levels in a transgenic mouse model of AD (Tg PS1/APPsw) and improved Aβ clearance across the blood-brain barrier (BBB), whereas amlodipine and nifedipine were ineffective showing that the Aβ-lowering activity of the DHPs is independent of their antihypertensive activity. Chronic oral treatment with nilvadipine decreased Aβ burden in the brains of Tg APPsw (Tg2576) and Tg PS1/APPsw mice, and also improved learning abilities and spatial memory. Our data suggest that the clinical benefit conferred by certain antihypertensive DHPs against AD is unrelated to their antihypertensive activity, but rely on their ability to lower brainaccumulation by affecting both Aβ production and Aβ clearance across the BBB.

  16. Accumulation of Metals in Juvenile Carp (Cyprinus carpio) Exposed to Sublethal Levels of Iron and Manganese: Survival, Body Weight and Tissue.

    Science.gov (United States)

    Harangi, Sándor; Baranyai, Edina; Fehér, Milán; Tóth, Csilla Noémi; Herman, Petra; Stündl, László; Fábián, István; Tóthmérész, Béla; Simon, Edina

    2017-05-01

    Many oxbows are contaminated by Fe and Mn as a consequence of the elemental concentration of sediment and water originating from the Upper Tisza Region of Hungary. The phenomenon is partly caused by anthropogenic activities and mainly due to the geochemical characteristics of the region. The effects of Fe and Mn on the aquatic ecosystem of these wetlands were investigated in a model experiments in this study. Survival, individual body weight and the elemental concentrations of organs were determined in common carp (Cyprinus carpio) juveniles reared in Fe and Mn contaminated media (treatment 1: Fe 0.57 mg L -1 , Mn 0.29 mg L -1 , treatment 2: Fe 0.57 mg L -1 , Mn 0.625 mg L -1 , treatment 3: Fe 1.50 mg L -1 , Mn 0.29 mg L -1 , treatment 4: Fe 1.50 mg L -1 , Mn 0.625 mg L -1 and control: Fe 0.005 mg L -1 , Mn 0.003 mg L -1 ), for rearing time of 49 days. The treatment with Fe and Mn did not have any effect on the survival data and individual body weight in the levels tested. The highest concentration of Fe and Mn was found in the liver and brain of carp juveniles, while the lowest concentration of these elements occurred in the muscular tissue and gills. The treatment where Fe and Mn were applied in the highest concentrations resulted in a statistically higher level of these elements in the brain, grills and muscle tissues. The treatment where only Mn was present in the highest concentration caused increased level of Mn only in the liver. We found metal accumulation in almost every organ; however, the applied concentrations and exposure time did not affect the survival and average body weight of carp juveniles.

  17. Imaging brain iron and diffusion patterns: a follow-up study of Parkinson's disease in the initial stages.

    Science.gov (United States)

    Rossi, Maija Elina; Ruottinen, Hanna; Saunamäki, Tiia; Elovaara, Irina; Dastidar, Prasun

    2014-01-01

    The aim of this study was to examine changes of brain iron content and diffusion patterns longitudinally in early-stage Parkinson's disease (PD) patients using T2- and T2*-based magnetic resonance imaging (MRI) over 2-year follow-up. We imaged 32 PD patients with tremor and 19 healthy controls. A follow-up study (median 25 months, range 22-31 months) was accomplished for 25 patients (men:women = 11:14; age range 44-87 years, median 73 years). All patients and healthy volunteers underwent clinical, neuropsychological, and MRI examinations on the same day. Three different MRI sequences were used and their results were compared: T2-weighted imaging, susceptibility-weighted imaging, and T2* mapping. Additionally, we evaluated diffusion tensor data between groups using tract-based spatial statistics. Over the 2-year follow-up, the iron-related relaxation increased in the globus pallidus anterior and the caudate nucleus and slightly in the substantia nigra pars compacta (SNc). In the globus pallidus anterior and medial SNc, the change was associated with mild cognitive impairment. In the caudate nucleus, the increase was pronounced in patients with disease onset at 67 years or older. In the SNc, medial transverse relaxation was increased, and in the thalamus, it was decreased, in patients with PD compared with healthy volunteers at 2-year follow-up. Tract-based spatial statistical data did not differ between groups based on gender or Unified Parkinson's Disease Rating Scale, but a slight tendency to decreasing fractional anisotropy (P MRI sequences. Rather than correlating with disease duration, the rate of changes was associated with individual characters, such as cognitive decline and age. Copyright © 2014 AUR. Published by Elsevier Inc. All rights reserved.

  18. Amyloid-β Precursor Protein Modulates the Sorting of Testican-1 and Contributes to Its Accumulation in Brain Tissue and Cerebrospinal Fluid from Patients with Alzheimer Disease.

    Science.gov (United States)

    Barrera-Ocampo, Alvaro; Arlt, Sönke; Matschke, Jakob; Hartmann, Ursula; Puig, Berta; Ferrer, Isidre; Zürbig, Petra; Glatzel, Markus; Sepulveda-Falla, Diego; Jahn, Holger

    2016-09-01

    The mechanisms leading to amyloid-β (Aβ) accumulation in sporadic Alzheimer disease (AD) are unknown but both increased production or impaired clearance likely contribute to aggregation. To understand the potential roles of the extracellular matrix proteoglycan Testican-1 in the pathophysiology of AD, we used samples from AD patients and controls and an in vitro approach. Protein expression analysis showed increased levels of Testican-1 in frontal and temporal cortex of AD patients; histological analysis showed that Testican-1 accumulates and co-aggregates with Aβ plaques in the frontal, temporal and entorhinal cortices of AD patients. Proteomic analysis identified 10 fragments of Testican-1 in cerebrospinal fluid (CSF) from AD patients. HEK293T cells expressing human wild type or mutant Aβ precursor protein (APP) were transfected with Testican-1. The co-expression of both proteins modified the sorting of Testican-1 into the endocytic pathway leading to its transient accumulation in Golgi, which seemed to affect APP processing, as indicated by reduced Aβ40 and Aβ42 levels in APP mutant cells. In conclusion, patient data reflect a clearance impairment that may favor Aβ accumulation in AD brains and our in vitro model supports the notion that the interaction between APP and Testican-1 may be a key step in the production and aggregation of Aβ species. © 2016 Oxford University Press OR American Association of Neuropathologists.

  19. Neuronal Cholesterol Accumulation Induced by Cyp46a1 Down-Regulation in Mouse Hippocampus Disrupts Brain Lipid Homeostasis

    Directory of Open Access Journals (Sweden)

    Sophie Ayciriex

    2017-07-01

    Full Text Available Impairment in cholesterol metabolism is associated with many neurodegenerative disorders including Alzheimer's disease (AD. However, the lipid alterations underlying neurodegeneration and the connection between altered cholesterol levels and AD remains not fully understood. We recently showed that cholesterol accumulation in hippocampal neurons, induced by silencing Cyp46a1 gene expression, leads to neurodegeneration with a progressive neuronal loss associated with AD-like phenotype in wild-type mice. We used a targeted and non-targeted lipidomics approach by liquid chromatography coupled to high-resolution mass spectrometry to further characterize lipid modifications associated to neurodegeneration and cholesterol accumulation induced by CYP46A1 inhibition. Hippocampus lipidome of normal mice was profiled 4 weeks after cholesterol accumulation due to Cyp46a1 gene expression down-regulation at the onset of neurodegeneration. We showed that major membrane lipids, sphingolipids and specific enzymes involved in phosphatidylcholine and sphingolipid metabolism, were rapidly increased in the hippocampus of AAV-shCYP46A1 injected mice. This lipid accumulation was associated with alterations in the lysosomal cargoe, accumulation of phagolysosomes and impairment of endosome-lysosome trafficking. Altogether, we demonstrated that inhibition of cholesterol 24-hydroxylase, key enzyme of cholesterol metabolism leads to a complex dysregulation of lipid homeostasis. Our results contribute to dissect the potential role of lipids in severe neurodegenerative diseases like AD.

  20. Early Development of Parvalbumin-, Somatostatin-, and Cholecystokinin-Expressing Neurons in Rat Brain following Prenatal Immune Activation and Maternal Iron Deficiency.

    Science.gov (United States)

    Boksa, Patricia; Zhang, Ying; Nouel, Dominique; Wong, Alice; Wong, Tak Pan

    2016-01-01

    Prenatal maternal infection and maternal iron deficiency during pregnancy are 2 early environmental insults associated with increased risk for schizophrenia in offspring. Substantial evidence suggests that abnormalities in inhibitory γ-aminobutyric acid (GABA) interneuron function, especially in the parvalbumin subtype of GABA interneuron, both developmentally and in adulthood, may contribute mechanistically to cognitive deficits and psychotic symptoms in schizophrenia. This study used a rat model to test whether prenatal immune activation with lipopolysaccharide (LPS; at gestation days, GD, 15 and 16) or maternal iron deficiency (from GD2 to postnatal day P7) or the combination of both insults alters major subtypes of GABAergic interneurons (parvalbumin, somatostatin, cholecystokinin) in brain regions relevant to schizophrenia (medial and dorsolateral prefrontal cortex [PFC], hippocampal CA1 and dentate gyrus, ventral subiculum) in offspring at P14 or P28. Prenatal LPS treatment significantly increased the density of parvalbumin-immunoreactive neurons at P14 in the medial PFC, dorsolateral PFC, and ventral subiculum of offspring born from iron-sufficient but not iron-deficient dams. Prenatal LPS also increased cholecystokinin neuron density in the medial PFC at P28, under both iron-sufficient and iron-deficient conditions. We observed a large increase in parvalbumin neuron density from P14 to P28 in the medial PFC and subiculum across all birth groups, that was not observed in other brain regions, and significant decreases in somatostatin neuron density from P14 to P28 in all brain regions examined across all birth groups, indicating differential developmental trajectories for parvalbumin and somatostatin neurons in various brain regions during this early postnatal period. Thus, it appears that the medial PFC and ventral subiculum, brain regions involved in circuitry modulating ventral tegmental dopamine and nucleus accumbens activities, may be regions vulnerable

  1. Accumulation of 14C-5,6-dihydroxytryptamine-melanin in intrathecal and subependymal phagocytes of the rat CNS and possible routes of their elimination from brain

    Energy Technology Data Exchange (ETDEWEB)

    Baumgarten, H.G.; Moritz, F.; Schlossberger, H.G.

    1981-01-01

    14C-5,6-DHT-Melanin, a labelled synthetic polymer resembling the naturally occurring melanin formed in brain by autoxidation of dopamine, was injected into the left lateral ventricle of adult rats, and its fate followed by autoradiography and by transmission electron microscopy of structures identified as labelled in preceding light micrographs, and by EM-autoradiography. Shortly after injection, melanin particles (easily identified in the em because of their size, structure and electron opacity) were seen ingested by supraependymal and epiplexus cells, by cells residing in the piaarachnoid, i.e. free subarachnoidal cells and perivascular cells, and by subependymally located microglia-like cells with intraventricular processes. Up to day four, an increase in the number of labelled phagocytes in the CSF was noted which transformed into typical reactive macrophages. Beyond this time, many intraventricular melanin-loaded phagocytes formed rounded clusters; cells of such clusters were subsequently found to invade the brain parenchyma by penetrating the ependymal lining and to accumulate in the perivascular space of brain vessels. 14C-Melanin-storing macrophages were found in the marginal sinus of the deep jugular lymph nodes suggesting emigration of CNS-derived phagocytes via lymphatics or prelymphatics that contact the subarachnoidal space compartment. This does not exclude the possibility that some of the macrophages leave the brain via the systemic circulation by penetrating the vascular endothelium; these may be disposed of in peripheral organs other than the lymph nodes.

  2. Age-dependent memory loss, synaptic pathology and altered brain plasticity in the Drosophila mutant cardinal accumulating 3-hydroxykynurenine.

    Science.gov (United States)

    Savvateeva, E; Popov, A; Kamyshev, N; Bragina, J; Heisenberg, M; Senitz, D; Kornhuber, J; Riederer, P

    2000-01-01

    A search for Drosophila mutants with phenotypes similar to human diseases might help to unravel evolutionary conserved genes implicated in polygenic human disorders. Among these are neurodegenerative diseases, characterized by a late onset disturbance of memory, synaptic and glial pathology, structural brain impairments and altered content of the intermediates of the kynurenine pathway, the modulators of glutamate excito- and oxidative toxicity. This pathway is conserved in insects, in rodents, and in humans. We tested the Drosophila mutants cardinal (3-hydroxykynurenine excess) and cinnabar (kynurenic acid excess) for age-dependent changes in memory, synaptic pathology, structural brain plasticity and glial immunoreactivity. The mutant cardinal demonstrated a decline in learning and memory from the 12th to the 29th day of life in a paradigm of conditioned courtship suppression. Memory decline was accompanied by a sharp decrease in immunoreactivity to the synaptic cysteine string protein, and alterations in volumetric parameters of the mushroom bodies, the brain structures implicated in memory.

  3. The Mammalian “Obesogen” Tributyltin Targets Hepatic Triglyceride Accumulation and the Transcriptional Regulation of Lipid Metabolism in the Liver and Brain of Zebrafish

    Science.gov (United States)

    Lyssimachou, Angeliki; Santos, Joana G.; André, Ana; Soares, Joana; Lima, Daniela; Guimarães, Laura; Almeida, C. Marisa R.; Teixeira, Catarina; Castro, L. Filipe C.; Santos, Miguel M.

    2015-01-01

    Recent findings indicate that different Endocrine Disrupting Chemicals (EDCs) interfere with lipid metabolic pathways in mammals and promote fat accumulation, a previously unknown site of action for these compounds. The antifoulant and environmental pollutant tributyltin (TBT), which causes imposex in gastropod snails, induces an “obesogenic” phenotype in mammals, through the activation of the nuclear receptors retinoid X receptor (RXR) and peroxisome proliferator-activated receptor gamma (PPARγ). In teleosts, the effects of TBT on the lipid metabolism are poorly understood, particularly following exposure to low, environmental concentrations. In this context, the present work shows that exposure of zebrafish to 10 and 50 ng/L of TBT (as Sn) from pre-hatch to 9 months of age alters the body weight, condition factor, hepatosomatic index and hepatic triglycerides in a gender and dose related manner. Furthermore, TBT modulated the transcription of key lipid regulating factors and enzymes involved in adipogenesis, lipogenesis, glucocorticoid metabolism, growth and development in the brain and liver of exposed fish, revealing sexual dimorphic effects in the latter. Overall, the present study shows that the model mammalian obesogen TBT interferes with triglyceride accumulation and the transcriptional regulation of lipid metabolism in zebrafish and indentifies the brain lipogenic transcription profile of fish as a new target of this compound. PMID:26633012

  4. The Mammalian "Obesogen" Tributyltin Targets Hepatic Triglyceride Accumulation and the Transcriptional Regulation of Lipid Metabolism in the Liver and Brain of Zebrafish.

    Directory of Open Access Journals (Sweden)

    Angeliki Lyssimachou

    Full Text Available Recent findings indicate that different Endocrine Disrupting Chemicals (EDCs interfere with lipid metabolic pathways in mammals and promote fat accumulation, a previously unknown site of action for these compounds. The antifoulant and environmental pollutant tributyltin (TBT, which causes imposex in gastropod snails, induces an "obesogenic" phenotype in mammals, through the activation of the nuclear receptors retinoid X receptor (RXR and peroxisome proliferator-activated receptor gamma (PPARγ. In teleosts, the effects of TBT on the lipid metabolism are poorly understood, particularly following exposure to low, environmental concentrations. In this context, the present work shows that exposure of zebrafish to 10 and 50 ng/L of TBT (as Sn from pre-hatch to 9 months of age alters the body weight, condition factor, hepatosomatic index and hepatic triglycerides in a gender and dose related manner. Furthermore, TBT modulated the transcription of key lipid regulating factors and enzymes involved in adipogenesis, lipogenesis, glucocorticoid metabolism, growth and development in the brain and liver of exposed fish, revealing sexual dimorphic effects in the latter. Overall, the present study shows that the model mammalian obesogen TBT interferes with triglyceride accumulation and the transcriptional regulation of lipid metabolism in zebrafish and indentifies the brain lipogenic transcription profile of fish as a new target of this compound.

  5. Iron deposition in rabbit cerebellum after exposure to generated and mobile GSM electromagnetic fields.

    Science.gov (United States)

    Kopani, M; Filova, B; Sevcik, P; Kosnac, D; Misek, J; Polak, S; Kohan, M; Major, J; Zdimalova, M; Jakus, J

    2017-01-01

    Mobile phone application may cause structural, functional changes and accumulation of toxic elements in brain. The aim of this study was to investigate iron accumulation in rabbit cerebellum after exposure to RF EMF with light and scanning electron microscopy. Histochemical analysis of iron distribution by light and electron microscopy with energy-dispersive microanalysis was used. Light microscopy revealed dystrophic changes of Purkinje cells in irradiated groups and iron deposits located in various parts of cerebellum. Deposits consists of C, O, Na, Mg, Al, Si, P, S, Cl, Ca and Fe. Our experiment revealed structural changes of Purkinje cells and iron and aluminium accumulations in stratum granulosum of rabbit's cerebellum after exposure to RF EMF (Fig. 6, Ref. 33).

  6. Toxic synergism between quinolinic acid and organic acids accumulating in glutaric acidemia type I and in disorders of propionate metabolism in rat brain synaptosomes: Relevance for metabolic acidemias.

    Science.gov (United States)

    Colín-González, A L; Paz-Loyola, A L; Serratos, I; Seminotti, B; Ribeiro, C A J; Leipnitz, G; Souza, D O; Wajner, M; Santamaría, A

    2015-11-12

    The brain of children affected by organic acidemias develop acute neurodegeneration linked to accumulation of endogenous toxic metabolites like glutaric (GA), 3-hydroxyglutaric (3-OHGA), methylmalonic (MMA) and propionic (PA) acids. Excitotoxic and oxidative events are involved in the toxic patterns elicited by these organic acids, although their single actions cannot explain the extent of brain damage observed in organic acidemias. The characterization of co-adjuvant factors involved in the magnification of early toxic processes evoked by these metabolites is essential to infer their actions in the human brain. Alterations in the kynurenine pathway (KP) - a metabolic route devoted to degrade tryptophan to form NAD(+) - produce increased levels of the excitotoxic metabolite quinolinic acid (QUIN), which has been involved in neurodegenerative disorders. Herein we investigated the effects of subtoxic concentrations of GA, 3-OHGA, MMA and PA, either alone or in combination with QUIN, on early toxic endpoints in rat brain synaptosomes. To establish specific mechanisms, we pre-incubated synaptosomes with different protective agents, including the endogenous N-methyl-d-aspartate (NMDA) receptor antagonist kynurenic acid (KA), the antioxidant S-allylcysteine (SAC) and the nitric oxide synthase (NOS) inhibitor nitro-l-arginine methyl ester (l-NAME). While the incubation of synaptosomes with toxic metabolites at subtoxic concentrations produced no effects, their co-incubation (QUIN+GA, +3-OHGA, +MMA or +PA) decreased the mitochondrial function and increased reactive oxygen species (ROS) formation and lipid peroxidation. For all cases, this effect was partially prevented by KA and l-NAME, and completely avoided by SAC. These findings suggest that early damaging events elicited by organic acids involved in metabolic acidemias can be magnified by toxic synergism with QUIN, and this process is mostly mediated by oxidative stress, and in a lesser extent by excitotoxicity and

  7. Brain accumulation of myo-inositol in the trisomy 16 mouse, an animal model of Down's syndrome.

    OpenAIRE

    Shetty, H U; Holloway, H W; Acevedo, L D; Galdzicki, Z.

    1996-01-01

    myo-Inositol and several other polyols were measured in the tissues of the trisomy 16 mouse (animal model of Down's Syndrome; human trisomy 21) and diploid controls. myo-Inositol was found to be selectively elevated in the brain of the trisomy 16 mouse. However, peripheral tissues showed no elevation. These results are consistent with the cerebrospinal fluid and plasma data reported previously on myo-inositol in Down's Syndrome subjects.

  8. Targeting Cells With MR Imaging Probes: Cellular Interaction And Intracellular Magnetic Iron Oxide Nanoparticles Uptake In Brain Capillary Endothelial and Choroidal Plexus Epithelial Cells

    Science.gov (United States)

    Cambianica, I.; Bossi, M.; Gasco, P.; Gonzalez, W.; Idee, J. M.; Miserocchi, G.; Rigolio, R.; Chanana, M.; Morjan, I.; Wang, D.; Sancini, G.

    2010-10-01

    Magnetic iron oxide nanoparticles (NPs) are considered for various diagnostic and therapeutic applications in brain including their use as contrast agent for magnetic resonance imaging. In delivery application, the critical step is the transport across cell layers and the internalization of NPs into specific cells, a process often limited by poor targeting specificity and low internalization efficiency. The development of the models of brain endothelial cells and choroidal plexus epithelial cells in culture has allowed us to investigate into these mechanisms. Our strategy is aimed at exploring different routes to the entrapment of iron oxide NPs in these brain related cells. Here we demonstrated that not only cells endowed with a good phagocytic activity like activated macrophages but also endothelial brain capillary and choroidal plexus epithelial cells do internalize iron oxide NPs. Our study of the intracellular trafficking of NPs by TEM, and confocal microscopy revealed that NPs are mainly internalized by the endocytic pathway. Iron oxide NPs were dispersed in water and coated with 3,4-dihydroxyl-L-phenylalanine (L-DOPA) using standard procedures. Magnetic lipid NPs were prepared by NANOVECTOR: water in oil in water (W/O/W) microemulsion process has been applied to directly coat different iron based NPs by lipid layer or to encapsulate them into Solid Lipid Nanoparticles (SLNs). By these coating/loading the colloidal stability was improved without strong alteration of the particle size distribution. Magnetic lipid NPs could be reconstituted after freeze drying without appreciable changes in stability. L-DOPA coated NPs are stable in PBS and in MEM (Modified Eagle Medium) medium. The magnetic properties of these NPs were not altered by the coating processes. We investigated the cellular uptake, cytotoxicity, and interaction of these NPs with rat brain capillary endothelial (REB4) and choroidal plexus epithelial (Z310) cells. By means of widefield, confocal

  9. HO-1-mediated macroautophagy: a mechanism for unregulated iron deposition in aging and degenerating neural tissues.

    Science.gov (United States)

    Zukor, Hillel; Song, Wei; Liberman, Adrienne; Mui, Jeannie; Vali, Hojatollah; Fillebeen, Carine; Pantopoulos, Kostas; Wu, Ting-Di; Guerquin-Kern, Jean-Luc; Schipper, Hyman M

    2009-05-01

    Oxidative stress, deposition of non-transferrin iron, and mitochondrial insufficiency occur in the brains of patients with Alzheimer disease (AD) and Parkinson disease (PD). We previously demonstrated that heme oxygenase-1 (HO-1) is up-regulated in AD and PD brain and promotes the accumulation of non-transferrin iron in astroglial mitochondria. Herein, dynamic secondary ion mass spectrometry (SIMS) and other techniques were employed to ascertain (i) the impact of HO-1 over-expression on astroglial mitochondrial morphology in vitro, (ii) the topography of aberrant iron sequestration in astrocytes over-expressing HO-1, and (iii) the role of iron regulatory proteins (IRP) in HO-1-mediated iron deposition. Astroglial hHO-1 over-expression induced cytoplasmic vacuolation, mitochondrial membrane damage, and macroautophagy. HO-1 promoted trapping of redox-active iron and sulfur within many cytopathological profiles without impacting ferroportin, transferrin receptor, ferritin, and IRP2 protein levels or IRP1 activity. Thus, HO-1 activity promotes mitochondrial macroautophagy and sequestration of redox-active iron in astroglia independently of classical iron mobilization pathways. Glial HO-1 may be a rational therapeutic target in AD, PD, and other human CNS conditions characterized by the unregulated deposition of brain iron.

  10. Démantèlement des paysages cuirassés anciens en zones forestières tropicales d'Afrique centrale : formation d'accumulations ferrugineuses actuelles en bas de versantOld ferricrete landscape dismantling in Central Africa rain forest zone: formation of the present downslope iron accumulations

    Science.gov (United States)

    Temgoua, Émile; Bitom, Dieudonné; Bilong, Paul; Lucas, Yves; Pfeifer, Hans-Rudolf

    Present downslope iron accumulations were investigated in the rainforest zone in southern Cameroon. Six clay and Fe-hydroxide dominated patterns have been identified and occur on the lower part of hill slopes. They can be subdivided in three different sequences, related to gentle, moderate or steep slopes. They are discontinuous with respect to the dismantling zone of the old ferricrete cap formed at Cretaceous period. They show a gradual development from a soft Fe-crust (carapace) to a vesicular facies that will, with time, cover the whole landscape again. To cite this article: É. Temgoua et al., C. R. Geoscience 334 (2002) 537-543.

  11. Age- and stage-dependent accumulation of advanced glycation end products in intracellular deposits in normal and Alzheimer's disease brains.

    Science.gov (United States)

    Lüth, Hans-Joachim; Ogunlade, Vera; Kuhla, Björn; Kientsch-Engel, Rosemarie; Stahl, Peter; Webster, Julie; Arendt, Thomas; Münch, Gerald

    2005-02-01

    In this immunohistochemical study, the age- and stage-dependent accumulation of advanced glycation end-products (AGEs) in Alzheimer's disease (AD) and their relation to the formation of neurofibrillary tangles and neuronal cell death was investigated. For this purpose, the distribution of AGEs in neurons and glia was analyzed in the auditory association area of superior temporal gyrus (Brodmann area 22) of young and old non-demented controls and compared with early- and late-stage AD. A possible co-localization of AGEs with typical hallmarks of AD, such as hyperphosphorylated tau (as a marker for disturbed kinase/phosphatase activity), nNOS (as a marker for nitroxidative stress) and caspase-3 (as a marker of apoptotic cell death), was also investigated. Our results show that the percentage of AGE-positive neurons (and astroglia) increase both with age and, in AD patients, with the progression of the disease (Braak stages). Interestingly, nearly all if those neurons which show diffuse cytosolic AGE immunoreactivity also contain hyperphosphoryated tau, suggesting a link between AGE accumulation and the formation of early neurofibrillary tangles. Many, but not all, neurons show a co-localization of AGEs with other markers of neurodegeneration, such as nNOS and caspase-3.

  12. Effects on the accumulation of calcium, magnesium, iron, manganese, copper and zinc of adding the two inorganic forms of selenium to solution cultures of Zea mays.

    Science.gov (United States)

    Longchamp, M; Angeli, N; Castrec-Rouelle, M

    2016-01-01

    The addition of selenate or selenite to common fertilizers for crop production could be an effective way of producing selenium-rich food and feed. However, this would be feasible only if the increase in plant selenium (Se) content did not negatively influence the uptake of other essential elements. We therefore need to understand the interactions between Se and other major and trace elements during uptake by the plant. This study aimed to evaluate the influence of inorganic forms of Se on the accumulation of selected macronutrients (Ca and Mg) and micronutrients (Fe, Zn, Mn and Cu). Those essential elements are involved in the oxidative balance of cells. Zea mays seedlings were grown hydroponically in growth chambers in nutrient solutions to which we added 10, 50 or 1000 μg.L(-1) of selenate and/or selenite. Cation accumulation was significantly affected by the addition of 50 μg.L(-1) or 1000 μg.L(-1) Se, but not by the presence of 10 μg.L(-1) of Se in the nutrient solution. The highest concentration (1000 μg.L(-1)) of Se in the nutrient solution affected the accumulation of essential cations in Zea mays: selenate tended to increase the accumulation of Mg, Zn and Mn, whereas a selenate/selenite mixture tended to decrease the accumulation of Ca, Mg, Zn and Mn. Only Fe accumulation was unaffected by Se whatever its form or concentration. Selenium may also affect the distribution of cations on Zea mays. For example, levels of Mg and Zn translocation to the shoots were lower in the presence of selenite. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  13. Multicenter R2* mapping in the healthy brain

    DEFF Research Database (Denmark)

    Ropele, Stefan; Wattjes, Mike P; Langkammer, Christian

    2014-01-01

    PURPOSE: The R2* relaxation rate constant has been suggested as a sensitive measure for iron accumulation. The aim of this multi-center study was to assess the inter-scanner and inter-subject variability of R2* mapping and to investigate the relationship between brain volume and R2* in specific...

  14. A Potential Biomarker in Amyotrophic Lateral Sclerosis: Can Assessment of Brain Iron Deposition with SWI and Corticospinal Tract Degeneration with DTI Help?

    Science.gov (United States)

    Sheelakumari, R; Madhusoodanan, M; Radhakrishnan, A; Ranjith, G; Thomas, B

    2016-02-01

    Iron-mediated oxidative stress plays a pivotal role in the pathogenesis of amyotrophic lateral sclerosis. This study aimed to assess iron deposition qualitatively and quantitatively by using SWI and microstructural changes in the corticospinal tract by using DTI in patients with amyotrophic lateral sclerosis. Seventeen patients with amyotrophic lateral sclerosis and 15 age- and sex-matched controls underwent brain MR imaging with SWI and DTI. SWI was analyzed for both signal-intensity scoring and quantitative estimation of iron deposition in the anterior and posterior banks of the motor and sensory cortices and deep gray nuclei. The diffusion measurements along the corticospinal tract at the level of pons and medulla were obtained by ROI analysis. Patients with amyotrophic lateral sclerosis showed reduced signal-intensity grades in the posterior bank of the motor cortex bilaterally. Quantitative analysis confirmed significantly higher iron content in the posterior bank of the motor cortex in patients with amyotrophic lateral sclerosis. In contrast, no significant differences were noted for the anterior bank of the motor cortex, anterior and posterior banks of the sensory cortex, and deep nuclei. Receiver operating characteristic comparison showed a cutoff of 35μg Fe/g of tissue with an area under the curve of 0.78 (P = .008) for the posterior bank of the motor cortex in discriminating patients with amyotrophic lateral sclerosis from controls. Fractional anisotropy was lower in the pyramidal tracts of patients with amyotrophic lateral sclerosis at the pons and medulla on either side, along with higher directionally averaged mean diffusivity values. The combination of SWI and DTI revealed an area under the curve of 0.784 for differentiating patients with amyotrophic lateral sclerosis from controls. Measurements of motor cortex iron deposition and diffusion tensor parameters of the corticospinal tract may be useful biomarkers for the diagnosis of clinically suspected

  15. Increased iron accumulation occurs in the earliest stages of demyelinating disease: an ultra-high field susceptibility mapping study in Clinically Isolated Syndrome.

    Science.gov (United States)

    Al-Radaideh, Ali M; Wharton, Samuel J; Lim, Su-Yin; Tench, Christopher R; Morgan, Paul S; Bowtell, Richard W; Constantinescu, Cris S; Gowland, Penny A

    2013-06-01

    To determine, using ultra-high field magnetic resonance imaging (MRI), whether changes in iron content occur in the earliest phases of demyelinating disease, by quantifying the magnetic susceptibility of deep grey matter structures in patients with Clinically Isolated Syndrome (CIS) that is suggestive of multiple sclerosis (MS), as compared with age-matched healthy subjects. We compared 19 CIS patients to 20 age-matched, healthy controls. Scanning of the study subjects was performed on a 7T Philips Achieva system, using a 3-dimensional, T2*-weighted gradient echo acquisition. Phase data were first high-pass filtered, using a dipole fitting method, and then inverted to produce magnetic susceptibility maps. Region of interest (ROI) analysis was used to estimate magnetic susceptibility values for deep grey matter structures (caudate nucleus, putamen, globus pallidus, the thalamus and its pulvinar). Significantly increased relative susceptibilities were found in the CIS group, compared with controls, for the caudate nucleus (p = 0.05). In CIS patients, the time elapsed since the clinical event and the Expanded Disability Status Scale (EDSS) scores were not correlated with iron levels in any ROI (r(2) 0.05); however, a moderate correlation (r(2) = 0.3; p disease.

  16. Iron Deposition Is Positively Related to Cognitive Impairment in Patients with Chronic Mild Traumatic Brain Injury: Assessment with Susceptibility Weighted Imaging.

    Science.gov (United States)

    Lu, Liyan; Cao, Heli; Wei, Xiaoer; Li, Yuehua; Li, Wenbin

    2015-01-01

    This study aimed to evaluate the usability of SWI in assessment of brain iron to detect cognitive dysfunction in patients with chronic mild traumatic brain injury (mTBI). 39 patients with mTBI and 37 normal controls were given the Mini-Mental State Examination (MMSE) and underwent SWI scanning at least 6 months after injury. Angle radian values were calculated with phase images. The angle radian values were compared between groups using analysis of covariance, and their association with MMSE scores was analyzed using Spearman correlations. Significantly higher angle radian values (p radian values in the right substantia nigra (r = -0.685, p radian values in the right substantia nigra, suggesting a role of SWI in the assessment of cognitive impairments of these patients.

  17. In vivo assessment of iron content of the cerebral cortex in healthy aging using 7-Tesla T2*-weighted phase imaging.

    Science.gov (United States)

    Buijs, Mathijs; Doan, Nhat Trung; van Rooden, Sanneke; Versluis, Maarten J; van Lew, Baldur; Milles, Julien; van der Grond, Jeroen; van Buchem, Mark A

    2017-05-01

    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. The cortex was automatically segmented and parcellated, and phase shift was analyzed using an in-house developed method. We found a significant increase in phase shift with age in 20 of 22 cortical regions, concurrent with current understanding of cortical iron accumulation. Our findings suggest that increased cortical iron content can be assessed in healthy aging in vivo. The high spatial resolution and sensitivity to iron of our method make it a potentially useful tool for studying cortical iron accumulation in healthy aging and neurodegenerative diseases. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Combined deficiency of iron and (n-3) fatty acids in male rats disrupts brain monoamine metabolism and produces greater memory deficits than iron deficiency or (n-3) fatty acid deficiency alone.

    Science.gov (United States)

    Baumgartner, Jeannine; Smuts, Cornelius M; Malan, Linda; Arnold, Myrtha; Yee, Benjamin K; Bianco, Laura E; Boekschoten, Mark V; Müller, Michael; Langhans, Wolfgang; Hurrell, Richard F; Zimmermann, Michael B

    2012-08-01

    Deficiencies of iron (Fe) (ID) and (n-3) fatty acids (FA) [(n-3)FAD] may impair brain development and function through shared mechanisms. However, little is known about the potential interactions between these 2 common deficiencies. We studied the effects of ID and (n-3)FAD, alone and in combination, on brain monoamine pathways (by measuring monoamines and related gene expression) and spatial working and reference memory (by Morris water maze testing). Using a 2 × 2 design, male rats were fed an ID, (n-3)FAD, ID+(n-3)FAD, or control diet for 5 wk postweaning (postnatal d 21-56) after (n-3)FAD had been induced over 2 generations. The (n-3)FAD and ID diets decreased brain (n-3) FA by 70-76% and Fe by 20-32%, respectively. ID and (n-3)FAD significantly increased dopamine (DA) concentrations in the olfactory bulb (OB) and striatum, with an additive 1- to 2-fold increase in ID+(n-3)FAD rats compared with controls (P working memory performance and the impairment positively correlated with DA concentrations in FC (r = 0.39; P = 0.026). Reference memory was impaired in the ID+(n-3)FAD rats (P memory than ID or (n-3)FAD alone.

  19. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... Follow a very low-fat diet over a long time. Some higher fat foods, like meat, are ... iron deficiency during infancy and childhood can have long-lasting, negative effects on brain health, the American ...

  20. Iron deficiency in childhood

    NARCIS (Netherlands)

    Uijterschout, L.

    2015-01-01

    Iron deficiency (ID) is the most common micronutrient deficiency in the world. Iron is involved in oxygen transport, energy metabolism, immune response, and plays an important role in brain development. In infancy, ID is associated with adverse effects on cognitive, motor, and behavioral development

  1. Role of Caspase-3-Mediated Apoptosis in Chronic Caspase-3-Cleaved Tau Accumulation and Blood-Brain Barrier Damage in the Corpus Callosum after Traumatic Brain Injury in Rats.

    Science.gov (United States)

    Glushakova, Olena Y; Glushakov, Andriy O; Borlongan, Cesar V; Valadka, Alex B; Hayes, Ronald L; Glushakov, Alexander V

    2017-07-21

    Traumatic brain injury (TBI) may be a significant risk factor for development of neurodegenerative disorders such as chronic traumatic encephalopathy (CTE), post-traumatic epilepsy (PTE), and Alzheimer's (AD) and Parkinson's (PD) diseases. Chronic TBI is associated with several pathological features that are also characteristic of neurodegenerative diseases, including tau pathologies, caspase-3-mediated apoptosis, neuroinflammation, and microvascular alterations. The goal of this study was to evaluate changes following TBI in cleaved-caspase-3 and caspase-3-cleaved tau truncated at Asp421, and their relationships to cellular markers potentially associated with inflammation and blood-brain (BBB) barrier damage. We studied astrocytes (glial fibrillary acidic protein [GFAP]), microglia (ionized calcium-binding adapter molecule 1 [Iba1]), BBB (endothelial barrier antigen [EBA]), and activated microglia/macrophages (cluster of differentiation 68 [CD68]). We employed immunohistochemistry at different time points from 24 h to 3 months after controlled cortical impact (CCI) injury in rats, with particular interest in white matter. The study demonstrated that CCI caused chronic upregulation of cleaved-caspase-3 in the white matter of the corpus callosum. Increases in cleaved-caspase-3 in the corpus callosum were accompanied by accumulation of caspase-3-cleaved tau, with increasing perivascular aggregation 3 months after CCI. Immunofluorescence experiments further showed cellular co-localization of cleaved-caspase-3 with GFAP and CD68 and its adjacent localization with EBA, suggesting involvement of apoptosis and neuroinflammation in mechanisms of delayed BBB and microvascular damage that could contribute to white matter changes. This study also provides the first evidence that evolving upregulation of cleaved-caspase-3 is associated with accumulation of caspase-3-cleaved tau following experimental TBI, thus providing new insights into potential common mechanisms mediated

  2. Iron Chelation

    Science.gov (United States)

    Skip to main content Menu Donate Treatments Therapies Iron Chelation Iron chelation therapy is the main treatment ... have iron overload and need treatment. What is iron overload? Iron chelation therapy is used when you ...

  3. RanBP9 overexpression down-regulates phospho-cofilin, causes early synaptic deficits and impaired learning, and accelerates accumulation of amyloid plaques in the mouse brain.

    Science.gov (United States)

    Palavicini, Juan Pablo; Wang, Hongjie; Minond, Dmitriy; Bianchi, Elisabetta; Xu, Shaohua; Lakshmana, Madepalli K

    2014-01-01

    Loss of synaptic proteins and functional synapses in the brains of patients with Alzheimer's disease (AD) as well as transgenic mouse models expressing amyloid-β protein precursor is now well established. However, the earliest age at which such loss of synapses occurs, and whether known markers of AD progression accelerate functional deficits is completely unknown. We previously showed that RanBP9 overexpression leads to enhanced amyloid plaque burden in a mouse model of AD. In this study, we found significant reductions in the levels of synaptophysin and spinophilin, compared with wild-type controls, in both the cortex and the hippocampus of 5- and 6-month old but not 3- or 4-month old APΔE9/RanBP9 triple transgenic mice, and not in APΔE9 double transgenic mice, nor in RanBP9 single transgenic mice. Interestingly, amyloid plaque burden was also increased in the APΔE9/RanBP9 mice at 5-6 months. Consistent with these results, we found significant deficits in learning and memory in the APΔE9/RanBP9 mice at 5 and 6 month. These data suggest that increased amyloid plaques and accelerated learning and memory deficits and loss of synaptic proteins induced by RanBP9 are correlated. Most importantly, APΔE9/RanBP9 mice also showed significantly reduced levels of the phosphorylated form of cofilin in the hippocampus. Taken together these data suggest that RanBP9 overexpression down-regulates cofilin, causes early synaptic deficits and impaired learning, and accelerates accumulation of amyloid plaques in the mouse brain.

  4. Contrasting effect of silicon on iron, zinc and manganese status and accumulation of metal-mobilizing compounds in micronutrient-deficient cucumber.

    Science.gov (United States)

    Bityutskii, Nikolai; Pavlovic, Jelena; Yakkonen, Kirill; Maksimović, Vuk; Nikolic, Miroslav

    2014-01-01

    Although the beneficial role of silicon (Si) in alleviation of abiotic stress is well established, little is known of the relevance of Si nutrition under microelement deficiency. The aim of our work was to investigate the physiological role of Si in relation to micronutrient (Fe, Zn and Mn) deficiencies in cucumber (Cucumis sativus L.). Cucumber (cv. Semkross) plants were grown hydroponically in a complete nutrient solution (control) and in nutrient solutions free from Fe, Zn or Mn, with or without Si supply. Plant tissue concentrations of microelements, organic acids and phenolics were measured. Si supply effectively mitigated the symptoms of Fe deficiency, but only in part, the symptoms of Zn- or Mn deficiency. Leaf Fe concentration significantly increased in plants deprived of Fe but treated with Si, whereas the concentrations of other microelements were not affected by Si supply. The effects of Si supply in increasing accumulation of both organic acids and phenolic compounds in cucumber tissues were exclusively related to Fe nutrition. Enhancement of Fe distribution towards apical shoot parts, along with the tissue accumulation of Fe-mobilizing compounds such as citrate (in leaves and roots) or cathechin (in roots) appears to be the major alleviating effect of Si. Si nutrition, however, was without effect on the mobility and tissue distribution of either Zn or Mn. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  5. Mining iron: iron uptake and transport in plants.

    Science.gov (United States)

    Kim, Sun A; Guerinot, Mary Lou

    2007-05-25

    Iron uptake in plants is highly regulated in order to supply amounts sufficient for optimal growth while preventing excess accumulation. In response to iron deficiency, plants induce either reduction-based or chelation-based mechanisms to enhance iron uptake from the soil. Genes involved in each mechanism have been identified from various model plants including Arabidopsis and rice. Iron transport within plants is also tightly controlled. New information has emerged on transporters that play a role in xylem loading and phloem loading/unloading of iron, and on the iron chelators involved in iron homeostasis. Some of the components regulating iron deficiency responses also have been elucidated, demonstrating that iron dependent gene regulation occurs at both the transcriptional and post-transcriptional levels.

  6. Intestinal Iron Homeostasis and Colon Tumorigenesis

    Directory of Open Access Journals (Sweden)

    Yatrik M. Shah

    2013-06-01

    Full Text Available Colorectal cancer (CRC is the third most common cause of cancer-related deaths in industrialized countries. Understanding the mechanisms of growth and progression of CRC is essential to improve treatment. Iron is an essential nutrient for cell growth. Iron overload caused by hereditary mutations or excess dietary iron uptake has been identified as a risk factor for CRC. Intestinal iron is tightly controlled by iron transporters that are responsible for iron uptake, distribution, and export. Dysregulation of intestinal iron transporters are observed in CRC and lead to iron accumulation in tumors. Intratumoral iron results in oxidative stress, lipid peroxidation, protein modification and DNA damage with consequent promotion of oncogene activation. In addition, excess iron in intestinal tumors may lead to increase in tumor-elicited inflammation and tumor growth. Limiting intratumoral iron through specifically chelating excess intestinal iron or modulating activities of iron transporter may be an attractive therapeutic target for CRC.

  7. Inversion recovery ultrashort echo time magnetic resonance imaging: A method for simultaneous direct detection of myelin and high signal demonstration of iron deposition in the brain - A feasibility study.

    Science.gov (United States)

    Sheth, Vipul R; Fan, Shujuan; He, Qun; Ma, Yajun; Annese, Jacopo; Switzer, Robert; Corey-Bloom, Jody; Bydder, Graeme M; Du, Jiang

    2017-05-01

    Multiple sclerosis (MS) causes demyelinating lesions in the white matter and increased iron deposition in the subcortical gray matter. Myelin protons have an extremely short T2* (brain of healthy volunteers shows a rapid signal decay with a short T2* of ~300μs, consistent with the T2* values of myelin protons in the synthetic myelin phantom. IR-UTE imaging in MS brain specimens and patients showed multiple white matter lesions as well as areas of high signal in subcortical gray matter. This in specimens corresponded in position to Perl's diaminobenzide staining results, consistent with increased iron deposition. IR-UTE imaging simultaneously detects lesions with myelin loss in the white matter and iron deposition in the gray matter. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Colloidal stability, surface characterisation and intracellular accumulation of Rhodium(II) citrate coated superparamagnetic iron oxide nanoparticles in breast tumour: a promising platform for cancer therapy

    Energy Technology Data Exchange (ETDEWEB)

    Silva Nunes, Eloiza da [Universidade Federal de Goias, Campus Samambaia, Instituto de Quimica (Brazil); Lemos Brettas Carneiro, Marcella; Guirelli Simoes de Oliveira, Ricardo; Nair Bao, Sonia [Universidade de Brasilia (UnB), Instituto de Ciencias Biologicas (Brazil); Ribeiro de Souza, Aparecido, E-mail: ardsouza@quimica.ufg.br [Universidade Federal de Goias, Campus Samambaia, Instituto de Quimica (Brazil)

    2013-06-15

    The colloidal stability of a rhodium(II) citrate, Rh{sub 2}(H{sub 2}cit){sub 4}, coating on the surface of maghemite ({gamma}-Fe{sub 2}O{sub 3}) nanoparticles was studied and compared in different dispersion media. The adsorption of Rh{sub 2}(H{sub 2}cit){sub 4} at the water-maghemite interface was evaluated as a function of pH and complex concentration. A slight pH-dependent adsorption of the complex was observed with a maximum at pH 3. The colloidal stability of the functionalised nanoparticles with different amounts of Rh{sub 2}(H{sub 2}cit){sub 4} as a function of pH was evaluated using dynamic light scattering measurements. The particles have a mean magnetic core size of 5.6 nm and the hydrodynamic diameters are approximately 60 nm, which remained unchanged in the pH range in which the samples were a stable sol. The tolerance to different dispersion media, which were deionised water, saline, phosphate-buffered saline (PBS), foetal bovine serum (FBS) and NaCl solutions with different concentrations, was investigated. At moderate ionic strength, the colloidal stability of the dispersions was similar in saline and in PBS compared to the stability of dispersions diluted in water. Moreover, the intracellular accumulation of nanoparticles in 4T1 breast tumour was examined by ultrastructural analysis performed by transmission electron microscopy. The rhodium(II) citrate-coated nanoparticles were found mostly in the cytoplasm and nucleus. Thus, we suggest that these SPIO nanoparticles functionalized with Rh{sub 2}(H{sub 2}Cit){sub 4} can be potential tools for anticancer therapy.

  9. One-pot synthesis of water-soluble superparamagnetic iron oxide nanoparticles and their MRI contrast effects in the mouse brains.

    Science.gov (United States)

    Wang, Jun; Zhang, Baolin; Wang, Lei; Wang, Ming; Gao, Fabao

    2015-03-01

    Water-soluble superparamagnetic iron oxide nanoparticles (SPIONs) were synthesized by the thermal decomposition of iron (III) acetylacetonate (Fe(acac)3) in the mixture of poly(ethylene glycol) (PEG) and poly(ethylene imine) (PEI). The average sizes of the SPIONs are in the range of 6-12nm, which could be tuned by adjusting the synthesis temperature and molecular weight of PEI. Benefiting from the coating of hydrophilic PEG and PEI, the resulted SPIONs showed excellent colloidal stability in deionized water and other physiological buffers. The XRD patterns indicate that the obtained SPIONs are magnetite. The PEG/PEI-SPIONs exhibited high r2/r1 ratio. In vivo magnetic resonance imaging (MRI) of the mouse brains after intravenous injection of the SPIONs showed their good contrast effect. Considering the facile fabrication process and excellent imaging performance of the water soluble PEG-SPIONs and PEG/PEI-SPIONs, it is believed that the SPIONs will find great potential in advanced MRI. Copyright © 2014 Elsevier B.V. All rights reserved.

  10. Iron-induced neuronal damage in a rat model of post-traumatic stress disorder.

    Science.gov (United States)

    Zhao, Ming; Yu, Zhibo; Zhang, Yang; Huang, Xueling; Hou, Jingming; Zhao, YanGang; Luo, Wei; Chen, Lin; Ou, Lan; Li, Haitao; Zhang, Jiqiang

    2016-08-25

    Previous studies have shown that iron redistribution and deposition in the brain occurs in some neurodegenerative diseases, and oxidative damage due to abnormal iron level is a primary cause of neuronal death. In the present study, we used the single prolonged stress (SPS) model to mimic post-traumatic stress disorder (PTSD), and examined whether iron was involved in the progression of PTSD. The anxiety-like behaviors of the SPS group were assessed by the elevated plus maze (EPM) and open field tests, and iron levels were measured by inductively coupled plasma optical emission spectrometer (ICP-OES). Expression of glucocorticoid receptors and transferrin receptor 1 (TfR1) and ferritin (Fn) was detected by Western blot and immunohistochemistry in selected brain areas; TfR1 and Fn mRNA expression were detected by quantitative-polymerase chain reaction (Q-PCR). Ultrastructures of the hippocampus were observed under a transmission electron microscope. Our results showed that SPS exposure induced anxiety-like symptoms and increased the level of serum cortisol and the concentration of iron in key brain areas such as the hippocampus, prefrontal cortex, and striatum. The stress induced region-specific changes in both protein and mRNA levels of TfR1 and Fn. Moreover, swelling mitochondria and cell apoptosis were observed in neurons in brain regions with iron accumulation. We concluded that SPS stress increased iron in some cognition-related brain regions and subsequently cause neuronal injury, indicating that the iron may function in the pathology of PTSD. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  11. Misregulation of iron homeostasis in amyotrophic lateral sclerosis

    Directory of Open Access Journals (Sweden)

    Anna Gajowiak

    2016-06-01

    Full Text Available Iron is essential for all mammalian cells, but it is toxic in excess. Our understanding of molecular mechanisms ensuring iron homeostasis at both cellular and systemic levels has dramatically increased over the past 15 years. However, despite major advances in this field, homeostatic regulation of iron in the central nervous system (CNS requires elucidation. It is unclear how iron moves in the CNS and how its transfer to the CNS across the blood-brain and the blood-cerebrospinal fluid barriers, which separate the CNS from the systemic circulation, is regulated. Increasing evidence indicates the role of iron dysregulation in neuronal cell death observed in neurodegenerative diseases including amyotrophic lateral sclerosis (ALS. ALS is a progressive neurodegenerative disorder characterized by selective cortical czynand spinal motor neuron dysfunction that results from a complex interplay among various pathogenic factors including oxidative stress. The latter is known to strongly affect cellular iron balance, creating a vicious circle to exacerbate oxidative injury. The role of iron in the pathogenesis of ALS is confirmed by therapeutic effects of iron chelation in ALS mouse models. These models are of great importance for deciphering molecular mechanisms of iron accumulation in neurons. Most of them consist of transgenic rodents overexpressing the mutated human superoxide dismutase 1 (SOD1 gene. Mutations in the SOD1 gene constituteone of the most common genetic causes of the inherited form of ALS. However, it should beconsidered that overexpression of the SOD1 gene usually leads to increased SOD1 enzymaticactivity, a condition which does not occur in human pathology and which may itself changethe expression of iron metabolism genes.

  12. Accumulation and Secretion of Coumarinolignans and other Coumarins in Arabidopsis thaliana Roots in Response to Iron Deficiency at High pH

    Directory of Open Access Journals (Sweden)

    Patricia Sisó-Terraza

    2016-11-01

    Full Text Available Root secretion of coumarin-phenolic type compounds has been recently shown to be related to Arabidopsis thaliana tolerance to Fe deficiency at high pH. These studies revealed the identity of a few simple coumarins occurring in roots and exudates of Fe-deficient A. thaliana plants, and left open the possible existence of other unknown phenolics. We used HPLC-UV-VIS-ESI-MS(TOF, HPLC/ESI-MSn(ion trap and HPLC-ESI-MS-MS(Q-TOF to characterize (identify and quantify phenolic-type compounds accumulated in roots or secreted into the nutrient solution of A. thaliana plants in response to Fe deficiency. Plants grown with or without Fe and using nutrient solutions buffered at pH 5.5 or 7.5 enabled to identify an array of phenolics. These include several coumarinolignans not previously reported in A. thaliana (cleomiscosins A, B, C and D and the 5’-hydroxycleomiscosins A and/or B, as well as some coumarin precursors (ferulic acid and coniferyl and sinapyl aldehydes, and previously reported cathecol (fraxetin and non-cathecol coumarins (scopoletin, isofraxidin and fraxinol, some of them in hexoside forms not previously characterized. The production and secretion of phenolics were more intense when the plant accessibility to Fe was diminished and the plant Fe status deteriorated, as it occurs when plants are grown in the absence of Fe at pH 7.5. Aglycones and hexosides of the four coumarins were abundant in roots, whereas only the aglycone forms could be quantified in the nutrient solution. A comprehensive quantification of coumarins, first carried out in this study, revealed that the catechol coumarin fraxetin was predominant in exudates (but not in roots of Fe-deficient A. thaliana plants grown at pH 7.5. Also, fraxetin was able to mobilize efficiently Fe from a Fe(III-oxide at pH 5.5 and pH 7.5. On the other hand, non-catechol coumarins were much less efficient in mobilizing Fe and were present in much lower concentrations, making unlikely that they

  13. Influence of Iron Supplementation on DMT1 (IRE)-induced Transport of Lead by Brain Barrier Systems in vivo.

    Science.gov (United States)

    An, Dai Zhi; Ai, Jun Tao; Fang, Hong Juan; Sun, Ru Bao; Shi, Yun; Wang, Li Li; Wang, Qiang

    2015-09-01

    To investigate the potential involvement of DMT1 (IRE) protein in the brain vascular system in vivo during Pb exposure. Three groups of male Sprague-Dawley rats were exposed to Pb in drinking water, among which two groups were concurrently administered by oral gavage once every other day as the low and high Fe treatment group, respectively, for 6 weeks. At the same time, the group only supplied with high Fe was also set as a reference. The animals were decapitated, then brain capillary-rich fraction was isolate from cerebral cortex. Western blot method was used to identify protein expression, and RT-PCR to detect the change of the mRNA. Pb exposure significantly increased Pb concentrations in cerebral cortex. Low Fe dose significantly reduced the cortex Pb levels, However, high Fe dose increased the cortex Pb levels. Interestingly, changes of DMT1 (IRE) protein in brain capillary-rich fraction were highly related to the Pb level, but those of DMT1 (IRE) mRNA were not significantly different. Moreover, the consistent changes in the levels of p-ERK1/2 or IRP1 with the changes in the levels of DMT1 (IRE). These results suggest that Pb is transported into the brain through DMT1 (IRE), and the ERK MAPK pathway is involved in DMT1 (IRE)-mediated transport regulation in brain vascular system in vivo. Copyright © 2015 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.

  14. Iron imaging reveals tumor and metastasis macrophage hemosiderin deposits in breast cancer.

    Science.gov (United States)

    Leftin, Avigdor; Ben-Chetrit, Nir; Klemm, Florian; Joyce, Johanna A; Koutcher, Jason A

    2017-01-01

    Iron-deposition is a metabolic biomarker of macrophages in both normal and pathological situations, but the presence of iron in tumor and metastasis-associated macrophages is not known. Here we mapped and quantified hemosiderin-laden macrophage (HLM) deposits in murine models of metastatic breast cancer using iron and macrophage histology, and in vivo MRI. Iron MRI detected high-iron pixel clusters in mammary tumors, lung metastasis, and brain metastasis as well as liver and spleen tissue known to contain the HLMs. Iron histology showed these regions to contain clustered macrophages identified by their common iron status and tissue-intrinsic association with other phenotypic macrophage markers. The in vivo MRI and ex vivo histological images were further processed to determine the frequencies and sizes of the iron deposits, and measure the number of HLMs in each deposit to estimate the in vivo MRI sensitivity for these cells. Hemosiderin accumulation is a macrophage biomarker and intrinsic contrast source for cellular MRI associated with the innate function of macrophages in iron metabolism systemically, and in metastatic cancer.

  15. Molecular mechanisms of non-transferrin-bound and transferring-bound iron uptake in primary hippocampal neurons.

    Science.gov (United States)

    Ji, Changyi; Kosman, Daniel J

    2015-06-01

    The molecular mechanisms of iron trafficking in neurons have not been elucidated. In this study, we characterized the expression and localization of ferrous iron transporters Zip8, Zip14 and divalent metal transporter 1 (DMT1), and ferrireductases Steap2 and stromal cell-derived receptor 2 in primary rat hippocampal neurons. Steap2 and Zip8 partially co-localize, indicating these two proteins may function in Fe(3+) reduction prior to Fe(2+) permeation. Zip8, DMT1, and Steap2 co-localize with the transferrin receptor/transferrin complex, suggesting they may be involved in transferrin receptor/transferrin-mediated iron assimilation. In brain interstitial fluid, transferring-bound iron (TBI) and non-transferrin-bound iron (NTBI) exist as potential iron sources. Primary hippocampal neurons exhibit significant iron uptake from TBI (Transferrin-(59) Fe(3+)) and NTBI, whether presented as (59) Fe(2+) -citrate or (59) Fe(3+) -citrate; reductase-independent (59) Fe(2+) uptake was the most efficient uptake pathway of the three. Kinetic analysis of Zn(2+) inhibition of Fe(2+) uptake indicated that DMT1 plays only a minor role in the uptake of NTBI. In contrast, localization and knockdown data indicate that Zip8 makes a major contribution. Data suggest also that cell accumulation of (59) Fe from TBI relies at least in part on an endocytosis-independent pathway. These data suggest that Zip8 and Steap2 play a major role in iron accumulation from NTBI and TBI by hippocampal neurons. Analysis of the expression and localization of known iron uptake transporters demonstrated that Zip8 makes a major contribution to iron accumulation in primary cultures of rat embryonic hippocampal neurons. These cells exhibit uptake pathways for ferrous and ferric iron (non-transferrin-bound iron, NTBI in figure) and for transferrin-bound iron; the ferrireductases Steap2 and SDR2 support the uptake of ferric iron substrates. Zip8 and Steap2 are strongly expressed in the plasma membrane of both soma

  16. immunohistochemical evaluation of iron accumulation in term ...

    African Journals Online (AJOL)

    ayferr

    2011-09-19

    Sep 19, 2011 ... Preeclampsia is a disease which involves hypertension and multisystem, it effects approximately 2 to. 8% of all pregnancies and is a significant cause of maternal and newborn mortality and morbidity. It develops in the placenta and its pathogenesis is associated with placental abnormalities. Classical.

  17. Brain tumor magnetic targeting and biodistribution of superparamagnetic iron oxide nanoparticles linked with 70-kDa heat shock protein study by nonlinear longitudinal response

    Energy Technology Data Exchange (ETDEWEB)

    Shevtsov, Maxim A., E-mail: shevtsov-max@mail.ru [Institute of Cytology of the Russian Academy of Sciences (RAS), Tikhoretsky Ave. 4, St. Petersburg 194064 (Russian Federation); A.L. Polenov Russian Research Scientific Institute of Neurosurgery, Mayakovsky str. 12, St. Petersburg 191014 (Russian Federation); Nikolaev, Boris P. [Research Institute of Highly Pure Biopreparations, Pudozhskaya str. 12, St. Petersburg 197110 (Russian Federation); Ryzhov, Vyacheslav A. [Petersburg Nuclear Physics Institute, NRC Kurchatov Institute, Gatchina 188300 (Russian Federation); Yakovleva, Ludmila Y. [Research Institute of Highly Pure Biopreparations, Pudozhskaya str. 12, St. Petersburg 197110 (Russian Federation); Dobrodumov, Anatolii V. [Institute of Macromolecular Compounds of the Russian Academy of Sciences (RAS), Bolshoi pr. 31, St. Petersburg 199004 (Russian Federation); Marchenko, Yaroslav Y. [Research Institute of Highly Pure Biopreparations, Pudozhskaya str. 12, St. Petersburg 197110 (Russian Federation); Margulis, Boris A. [Institute of Cytology of the Russian Academy of Sciences (RAS), Tikhoretsky Ave. 4, St. Petersburg 194064 (Russian Federation); Pitkin, Emil [The Wharton School, University of Pennsylvania, 3730 Walnut St., Philadelphia, PA 19104 (United States); Guzhova, Irina V. [Institute of Cytology of the Russian Academy of Sciences (RAS), Tikhoretsky Ave. 4, St. Petersburg 194064 (Russian Federation)

    2015-08-15

    Brain tumor targeting efficiency and biodistribution of the superparamagnetic nanoparticles conjugated with heat shock protein Hsp70 (SPION–Hsp70) were evaluated in experimental glioma model. Synthesized conjugates were characterized using the method of longitudinal nonlinear response of magnetic nanoparticles to a weak ac magnetic field with measurements of second harmonic of magnetization (NLR-M{sub 2}). Cellular interaction of magnetic conjugates was analyzed in 9L glioma cell culture. The biodistribution of the nanoparticles and their accumulation in tumors was assessed by the latter approach as well. The efficacy of Hsp70-conjugates for contrast enhancement in the orthotopic model of 9L glioma was assessed by MR imaging (11 T). Magnetic nanoparticles conjugated with Hsp70 had the relaxivity properties of the MR-negative contrast agents. Morphological observation and cell viability test demonstrated good biocompatibility of Hsp70-conjugates. Analysis of the T{sub 2}-weighted MR scans in tumor-bearing rats demonstrated the high efficacy of Hsp70-conjugates in contrast enhancement of the glioma in comparison to non-conjugated nanoparticles. High contrast enhancement of the glioma was provided by the accumulation of the SPION–Hsp70 particles in the glioma tissue (as shown by the histological assay). Biodistribution analysis by NLR-M{sub 2} measurements evidenced the many-fold increase (~40) in the tumor-to-normal brain uptake ratio in the Hsp70-conjugates treated animals. Biodistribution pattern of Hsp70-decorated nanoparticles differed from that of non-conjugated SPIONs. Coating of the magnetic nanoparticles with Hsp70 protein enhances the tumor-targeting ability of the conjugates that could be applied in the MR imaging of the malignant brain tumors. - Highlights: • Second-harmonic nonlinear magnetic response is used for biodistribution analysis. • NLR-M{sub 2} ensures high sensibility in detection of SPIONs in tissue. • SPION–Hsp70 conjugates

  18. Longitudinal tracking of human fetal cells labeled with super paramagnetic iron oxide nanoparticles in the brain of mice with motor neuron disease.

    Science.gov (United States)

    Bigini, Paolo; Diana, Valentina; Barbera, Sara; Fumagalli, Elena; Micotti, Edoardo; Sitia, Leopoldo; Paladini, Alessandra; Bisighini, Cinzia; De Grada, Laura; Coloca, Laura; Colombo, Laura; Manca, Pina; Bossolasco, Patrizia; Malvestiti, Francesca; Fiordaliso, Fabio; Forloni, Gianluigi; Morbidelli, Massimo; Salmona, Mario; Giardino, Daniela; Mennini, Tiziana; Moscatelli, Davide; Silani, Vincenzo; Cova, Lidia

    2012-01-01

    Stem Cell (SC) therapy is one of the most promising approaches for the treatment of Amyotrophic Lateral Sclerosis (ALS). Here we employed Super Paramagnetic Iron Oxide nanoparticles (SPIOn) and Hoechst 33258 to track human Amniotic Fluid Cells (hAFCs) after transplantation in the lateral ventricles of wobbler (a murine model of ALS) and healthy mice. By in vitro, in vivo and ex vivo approaches we found that: 1) the main physical parameters of SPIOn were maintained over time; 2) hAFCs efficiently internalized SPIOn into the cytoplasm while Hoechst 33258 labeled nuclei; 3) SPIOn internalization did not alter survival, cell cycle, proliferation, metabolism and phenotype of hAFCs; 4) after transplantation hAFCs rapidly spread to the whole ventricular system, but did not migrate into the brain parenchyma; 5) hAFCs survived for a long time in the ventricles of both wobbler and healthy mice; 6) the transplantation of double-labeled hAFCs did not influence mice survival.

  19. Longitudinal tracking of human fetal cells labeled with super paramagnetic iron oxide nanoparticles in the brain of mice with motor neuron disease.

    Directory of Open Access Journals (Sweden)

    Paolo Bigini

    Full Text Available Stem Cell (SC therapy is one of the most promising approaches for the treatment of Amyotrophic Lateral Sclerosis (ALS. Here we employed Super Paramagnetic Iron Oxide nanoparticles (SPIOn and Hoechst 33258 to track human Amniotic Fluid Cells (hAFCs after transplantation in the lateral ventricles of wobbler (a murine model of ALS and healthy mice. By in vitro, in vivo and ex vivo approaches we found that: 1 the main physical parameters of SPIOn were maintained over time; 2 hAFCs efficiently internalized SPIOn into the cytoplasm while Hoechst 33258 labeled nuclei; 3 SPIOn internalization did not alter survival, cell cycle, proliferation, metabolism and phenotype of hAFCs; 4 after transplantation hAFCs rapidly spread to the whole ventricular system, but did not migrate into the brain parenchyma; 5 hAFCs survived for a long time in the ventricles of both wobbler and healthy mice; 6 the transplantation of double-labeled hAFCs did not influence mice survival.

  20. Effects of novel neuroprotective and neurorestorative multifunctional drugs on iron chelation and glucose metabolism.

    Science.gov (United States)

    Pollak, Yulia; Mechlovich, Danit; Amit, Tamar; Bar-Am, Orit; Manov, Irena; Mandel, Silvia A; Weinreb, Orly; Meyron-Holtz, Esther G; Iancu, Theodore C; Youdim, Moussa B H

    2013-01-01

    Iron accumulation and iron-related oxidative stress are involved in several pathological conditions and provide a rationale for the development of iron chelators as novel promising therapeutic strategies. Thus, we have recently synthesized multifunctional non-toxic, brain permeable iron chelating compounds, M30 and HLA20, possessing the neuroprotective N-propargyl moiety of the anti-Parkinsonian drug, monoamine oxidase (MAO)-B inhibitor, rasagiline and the antioxidant-iron chelating moiety of an 8-hydroxyquinoline derivative of the iron chelator, VK28. Here, we examined the hepatic regulatory effects of these novel compounds using two experimental approaches: chelation activity and glucose metabolism parameters. The present study demonstrated that M30 and HLA20 significantly decreased intracellular iron content and reduced ferritin expression levels in iron-loaded hepatoma Hep3B cells. In electron microscopy analysis, M30 was shown to reduce the electron-dense deposits of siderosomes by ~30 %, as well as down-regulate cytosolic ferritin particles observed in iron-overloaded cells. In vivo studies demonstrated that M30 administration (1 mg/kg, P.O. three times a week) reduced hepatic ferritin levels; increased hepatic insulin receptor and glucose transporter-1 levels and improved glucose tolerance in C57BL/6 mice and in a mouse model of type-2 diabetes, the ob/ob (leptin(-/-)). The results clearly indicate that the novel multifunctional drugs, especially M30, display significant capacity of chelating intracellular iron and regulating glucose metabolism parameters. Such effects can have therapeutic significance in conditions with abnormal local or systemic iron metabolism, including neurological diseases.

  1. Brain region-specific perfluoroalkylated sulfonate (PFSA) and carboxylic acid (PFCA) accumulation and neurochemical biomarker responses in east Greenland polar bears (Ursus maritimus)

    DEFF Research Database (Denmark)

    Pedersen, Kathrine Eggers; Basu, Niladri; Letcher, Robert J.

    2015-01-01

    Perfluoroalkyl substances (PFASs) is a growing class of contaminants in the Arctic environment, and include the established perfluorinated sulfonates (PFSAs; especially perfluorooctane sulfonate (PFOS)) and carboxylic acids (PFCAs). PFSAs and PFCAs of varying chain length have been reported...... to bioaccumulate in lipid rich tissues of the brain among other tissues such as liver, and can reach high concentrations in top predators including the polar bear. PFCA and PFSA bioaccummulation in the brain has the potential to pose neurotoxic effects and therefore we conducted a study to investigate...

  2. Iron excretion in iron dextran-overloaded mice

    Science.gov (United States)

    Musumeci, Marco; Maccari, Sonia; Massimi, Alessia; Stati, Tonino; Sestili, Paola; Corritore, Elisa; Pastorelli, Augusto; Stacchini, Paolo; Marano, Giuseppe; Catalano, Liviana

    2014-01-01

    Background Iron homeostasis in humans is tightly regulated by mechanisms aimed to conserve iron for reutilisation, with a negligible role played by excretory mechanisms. In a previous study we found that mice have an astonishing ability to tolerate very high doses of parenterally administered iron dextran. Whether this ability is linked to the existence of an excretory pathway remains to be ascertained. Materials and methods Iron overload was generated by intraperitoneal injections of iron dextran (1 g/kg) administered once a week for 8 weeks in two different mouse strains (C57bl/6 and B6D2F1). Urinary and faecal iron excretion was assessed by inductively coupling plasma-mass spectrometry, whereas cardiac and liver architecture was evaluated by echocardiography and histological methods. For both strains, 24-hour faeces and urine samples were collected and iron concentration was determined on days 0, 1 and 2 after iron administration. Results In iron-overloaded C57bl/6 mice, the faecal iron concentration increased by 218% and 157% on days 1 and 2, respectively (p<0.01). The iron excreted represented a loss of 14% of total iron administered. Similar but smaller changes was also found in B6D2F1 mice. Conversely, we found no significant changes in the concentration of iron in the urine in either of the strains of mice. In both strains, histological examination showed accumulation of iron in the liver and heart which tended to decrease over time. Conclusions This study indicates that mice have a mechanism for removal of excess body iron and provides insights into the possible mechanisms of excretion. PMID:24960657

  3. Brain region-specific perfluoroalkylated sulfonate (PFSA) and carboxylic acid (PFCA) accumulation and neurochemical biomarker responses in east Greenland polar bears (Ursus maritimus).

    Science.gov (United States)

    Eggers Pedersen, Kathrine; Basu, Niladri; Letcher, Robert; Greaves, Alana K; Sonne, Christian; Dietz, Rune; Styrishave, Bjarne

    2015-04-01

    Perfluoroalkyl substances (PFASs) is a growing class of contaminants in the Arctic environment, and include the established perfluorinated sulfonates (PFSAs; especially perfluorooctane sulfonate (PFOS)) and carboxylic acids (PFCAs). PFSAs and PFCAs of varying chain length have been reported to bioaccumulate in lipid rich tissues of the brain among other tissues such as liver, and can reach high concentrations in top predators including the polar bear. PFCA and PFSA bioaccummulation in the brain has the potential to pose neurotoxic effects and therefore we conducted a study to investigate if variations in neurochemical transmitter systems i.e. the cholinergic, glutaminergic, dopaminergic and GABAergic, could be related to brain-specific bioaccumulation of PFASs in East Greenland polar bears. Nine brain regions from nine polar bears were analyzed for enzyme activity (monoamine oxidase (MAO), acetylcholinesterase (AChE) and glutamine synthetase (GS)) and receptor density (dopamine-2 (D2), muscarinic cholinergic (mAChR) and gamma-butyric acid type A (GABA-A)) along with PFSA and PFCA concentrations. Average brain ∑PFSA concentration was 25ng/g ww where PFOS accounted for 91%. Average ∑PFCA concentration was 88ng/g ww where PFUnDA, PFDoDA and PFTrDA combined accounted for 79%. The highest concentrations of PFASs were measured in brain stem, cerebellum and hippocampus. Correlative analyses were performed both across and within brain regions. Significant positive correlations were found between PFASs and MAO activity in occipital lobe (e.g. ∑PFCA; rp=0.83, p=0.041, n=6) and across brain regions (e.g. ∑PFCA; rp=0.47, p=0.001, ∑PFSA; rp=0.44, p>0.001; n=50). GABA-A receptor density was positively correlated with two PFASs across brain regions (PFOS; rp=0.33, p=0.02 and PFDoDA; rp=0.34, p=0.014; n=52). Significant negative correlations were found between mAChR density and PFASs in cerebellum (e.g. ∑PFCA; rp=-0.95, p=0.013, n=5) and across brain regions (e.g.

  4. Pulmonary Iron Homeostasis in Hepcidin Knockout Mice

    Directory of Open Access Journals (Sweden)

    Jean-Christophe Deschemin

    2017-10-01

    Full Text Available Pulmonary iron excess is deleterious and contributes to a range of chronic and acute inflammatory diseases. Optimal lung iron concentration is maintained through dynamic regulation of iron transport and storage proteins. The iron-regulatory hormone hepcidin is also expressed in the lung. In order to better understand the interactions between iron-associated molecules and the hepcidin-ferroportin axis in lung iron balance, we examined lung physiology and inflammatory responses in two murine models of systemic iron-loading, either hepcidin knock-out (Hepc KO or liver-specific hepcidin KO mice (Hepc KOliv, which do (Hepc KOliv or do not (Hepc KO express lung hepcidin. We have found that increased plasma iron in Hepc KO mice is associated with increased pulmonary iron levels, consistent with increased cellular iron uptake by pulmonary epithelial cells, together with an increase at the apical membrane of the cells of the iron exporter ferroportin, consistent with increased iron export in the alveoli. Subsequently, alveolar macrophages (AM accumulate iron in a non-toxic form and this is associated with elevated production of ferritin. The accumulation of iron in the lung macrophages of hepcidin KO mice contrasts with splenic and hepatic macrophages which contain low iron levels as we have previously reported. Hepc KOliv mice with liver-specific hepcidin deficiency demonstrated same pulmonary iron overload profile as the Hepc KO mice, suggesting that pulmonary hepcidin is not critical in maintaining local iron homeostasis. In addition, the high iron load in the lung of Hepc KO mice does not appear to enhance acute lung inflammation or injury. Lastly, we have shown that intraperitoneal LPS injection is not associated with pulmonary hepcidin induction, despite high levels of inflammatory cytokines. However, intranasal LPS injection stimulates a hepcidin response, likely derived from AM, and alters pulmonary iron content in Hepc KO mice.

  5. Iron excretion in iron dextran-overloaded mice.

    Science.gov (United States)

    Musumeci, Marco; Maccari, Sonia; Massimi, Alessia; Stati, Tonino; Sestili, Paola; Corritore, Elisa; Pastorelli, Augusto; Stacchini, Paolo; Marano, Giuseppe; Catalano, Liviana

    2014-10-01

    Iron homeostasis in humans is tightly regulated by mechanisms aimed to conserve iron for reutilisation, with a negligible role played by excretory mechanisms. In a previous study we found that mice have an astonishing ability to tolerate very high doses of parenterally administered iron dextran. Whether this ability is linked to the existence of an excretory pathway remains to be ascertained. Iron overload was generated by intraperitoneal injections of iron dextran (1 g/kg) administered once a week for 8 weeks in two different mouse strains (C57bl/6 and B6D2F1). Urinary and faecal iron excretion was assessed by inductively coupling plasma-mass spectrometry, whereas cardiac and liver architecture was evaluated by echocardiography and histological methods. For both strains, 24-hour faeces and urine samples were collected and iron concentration was determined on days 0, 1 and 2 after iron administration. In iron-overloaded C57bl/6 mice, the faecal iron concentration increased by 218% and 157% on days 1 and 2, respectively (piron excreted represented a loss of 14% of total iron administered. Similar but smaller changes was also found in B6D2F1 mice. Conversely, we found no significant changes in the concentration of iron in the urine in either of the strains of mice. In both strains, histological examination showed accumulation of iron in the liver and heart which tended to decrease over time. This study indicates that mice have a mechanism for removal of excess body iron and provides insights into the possible mechanisms of excretion.

  6. Effectiveness of micron-sized superparamagnetic iron oxide particles as markers for detection of migration of bone marrow-derived mesenchymal stromal cells in a stroke model.

    Science.gov (United States)

    Tarulli, Emidio; Chaudhuri, Joydeep D; Gretka, Voytek; Hoyles, Amy; Morshead, Cindi M; Stanisz, G J

    2013-06-01

    To evaluate the feasibility of using micron-sized superparamagnetic iron oxide particles (MPIOs) as an effective labeling agent for monitoring bone marrow-derived mesenchymal stromal cell (BMSC) migration in the brain using magnetic resonance imaging (MRI) in a rat model of stroke and whether the accumulation of MPIO-labeled BMSCs can be differentiated from the accumulation of free MPIO particles or hemoglobin breakdown at a site of neuronal damage. In this study BMSCs were labeled with iron oxide and their pattern of migration following intravenous injection in a rat stroke model was monitored using a clinical MRI system followed by standard histopathology. The migration pattern was compared between intravenous injection of BMSCs alone, BMSCs labeled with MPIOs, and MPIO particles alone. The results demonstrated that while MRI was highly sensitive in the detection of iron oxide particle-containing cells in areas of neuronal ischemia, the true origin of cells containing iron oxide particles remains ambiguous. Therefore, detection of iron particles may not be a suitable strategy for the detection of BMSCs in the brain in a stroke model. This study suggests that the use of MPIOs as labeling agents are insufficient to conclusively determine the localization of iron within cells in regions of neuronal ischemia and hemorrhage. Copyright © 2012 Wiley Periodicals, Inc.

  7. A cascade of iron-containing proteins governs the genetic iron starvation response to promote iron uptake and inhibit iron storage in fission yeast.

    Directory of Open Access Journals (Sweden)

    Javier Encinar del Dedo

    2015-03-01

    Full Text Available Iron is an essential cofactor, but it is also toxic at high levels. In Schizosaccharomyces pombe, the sensor glutaredoxin Grx4 guides the activity of the repressors Php4 and Fep1 to mediate a complex transcriptional response to iron deprivation: activation of Php4 and inactivation of Fep1 leads to inhibition of iron usage/storage, and to promotion of iron import, respectively. However, the molecular events ruling the activity of this double-branched pathway remained elusive. We show here that Grx4 incorporates a glutathione-containing iron-sulfur cluster, alone or forming a heterodimer with the BolA-like protein Fra2. Our genetic study demonstrates that Grx4-Fra2, but not Fep1 nor Php4, participates not only in iron starvation signaling but also in iron-related aerobic metabolism. Iron-containing Grx4 binds and inactivates the Php4 repressor; upon iron deprivation, the cluster in Grx4 is probably disassembled, the proteins dissociate, and Php4 accumulates at the nucleus and represses iron consumption genes. Fep1 is also an iron-containing protein, and the tightly bound iron is required for transcriptional repression. Our data suggest that the cluster-containing Grx4-Fra2 heterodimer constitutively binds to Fep1, and upon iron deprivation the disassembly of the iron cluster between Grx4 and Fra2 promotes reverse metal transfer from Fep1 to Grx4-Fra2, and de-repression of iron-import genes. Our genetic and biochemical study demonstrates that the glutaredoxin Grx4 independently governs the Php4 and Fep1 repressors through metal transfer. Whereas iron loss from Grx4 seems to be sufficient to release Php4 and allow its nuclear accumulation, total or partial disassembly of the Grx4-Fra2 cluster actively participates in iron-containing Fep1 activation by sequestering its iron and decreasing its interaction with promoters.

  8. Tissue levels of iron, copper, zinc and magnesium in iron deficient rats

    African Journals Online (AJOL)

    The effects of iron deficiency on the levels of iron, copper, zinc and magnesium in the brain, liver, kidney, heart and lungs of albino rats (Rattus novergicus) was investigated. Forty rats were divided into two groups and the first group was fed a control diet containing 1.09g iron/kg diet while the test group was fed diet ...

  9. Vitamin C deficiency in the brain impairs cognition, increases amyloid accumulation and deposition, and oxidative stress in APP/PSEN1 and normally aging mice.

    Science.gov (United States)

    Dixit, Shilpy; Bernardo, Alexandra; Walker, Jennifer Michelle; Kennard, John Andrew; Kim, Grace Youngeun; Kessler, Eric Sean; Harrison, Fiona Edith

    2015-04-15

    Subclinical vitamin C deficiency is widespread in many populations, but its role in both Alzheimer's disease and normal aging is understudied. In the present study, we decreased brain vitamin C in the APPSWE/PSEN1deltaE9 mouse model of Alzheimer's disease by crossing APP/PSEN1(+) bigenic mice with SVCT2(+/-) heterozygous knockout mice, which have lower numbers of the sodium-dependent vitamin C transporter required for neuronal vitamin C transport. SVCT2(+/-) mice performed less well on the rotarod task at both 5 and 12 months of age compared to littermates. SVCT2(+/-) and APP/PSEN1(+) mice and the combination genotype SVCT2(+/-)APP/PSEN1(+) were also impaired on multiple tests of cognitive ability (olfactory memory task, Y-maze alternation, conditioned fear, Morris water maze). In younger mice, both low vitamin C (SVCT2(+/-)) and APP/PSEN1 mutations increased brain cortex oxidative stress (malondialdehyde, protein carbonyls, F2-isoprostanes) and decreased total glutathione compared to wild-type controls. SVCT2(+/-) mice also had increased amounts of both soluble and insoluble Aβ1-42 and a higher Aβ1-42/1-40 ratio. By 14 months of age, oxidative stress levels were similar among groups, but there were more amyloid-β plaque deposits in both hippocampus and cortex of SVCT2(+/-)APP/PSEN1(+) mice compared to APP/PSEN1(+) mice with normal brain vitamin C. These data suggest that even moderate intracellular vitamin C deficiency plays an important role in accelerating amyloid pathogenesis, particularly during early stages of disease development, and that these effects are likely modulated by oxidative stress pathways.

  10. Native iron

    DEFF Research Database (Denmark)

    Brooks, Charles Kent

    2015-01-01

    , a situation unique in the Solar System. In such a world, iron metal is unstable and, as we all know, oxidizes to the ferric iron compounds we call 'rust'. If we require iron metal it must be produced at high temperatures by reacting iron ore, usually a mixture of ferrous (Fe2+) and ferric (Fe3+) oxides (Fe2O3......, hematite, or FeO.Fe2O3, magnetite), with carbon in the form of coke. This is carried out in a blast furnace. Although the Earth's core consists of metallic iron, which may also be present in parts of the mantle, this is inaccessible to us, so we must make our own. In West Greenland, however, some almost...... unique examples of iron metal, otherwise called 'native iron' or 'telluric iron', occur naturally....

  11. Iron Test

    Science.gov (United States)

    ... adrenocorticotropic hormone) can decrease them. Stress and sleep deprivation can temporarily decrease serum iron levels. Is iron ... Home About This Site Contact Us Terms Of Use In The News Policies Editorial Review Board Partner | ...

  12. New insights into early sequential PrPsc accumulation in scrapie infected mouse brain evidenced by the use of streptomycin sulfate.

    Science.gov (United States)

    Bencsik, Anna A; Leclere, Edwige; Perron, Hervé; Moussa, Aly

    2008-05-01

    To investigate the amplifying potentialities of streptomycin sulfate in the immunohistochemical (IHC) detection of the abnormal prion protein (PrPsc), we used a sequential brain sampling from C506M3 scrapie strain inoculated C57Bl/6 mice. The weekly removed brains, from 7 to 63 days post intra-cranial inoculation were analysed using PrPsc IHC. The introduction of streptomycin sulfate, a technique developed for accurate cellular and regional mapping of PrPsc deposition in several animal TSEs, revealed a substantial amplifying effect and a clear specific PrPsc detection as early as 28 days post inoculation. The location of the first detected PrPsc deposits suggests a possible involvement of the cerebrospinal fluid in the early dissemination of the infectious agent. The meaning of these newly accessible PrPsc deposits is discussed in relation to a possible nascent form of PrPsc molecules detected in situ for the first time. Altogether, these findings argue that this method can be highly useful to study the early stages after infection with prion agents.

  13. Nexus between mitochondrial function, iron, copper and glutathione in Parkinson's disease.

    Science.gov (United States)

    Liddell, Jeffrey R; White, Anthony R

    2017-05-31

    Parkinson's disease is neuropathologically characterised by loss of catecholamine neurons in vulnerable brain regions including substantia nigra pars compacta and locus coeruleus. This review discusses how the susceptibility of these regions is defined by their shared biochemical characteristics that differentiate them from other neurons. Parkinson's disease is biochemically characterised by mitochondrial dysfunction, accumulation of iron, diminished copper content and depleted glutathione levels in these regions. This review also discusses this neuropathology, and provides evidence for how these pathological features are mechanistically linked to each other. This leads to the conclusion that disruption of mitochondrial function, or iron, copper or glutathione metabolism in isolation provokes the pathological impairment of them all. This creates a vicious cycle that drives pathology leading to mitochondrial failure and neuronal cell death in vulnerable brain regions. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Differences in activation of mouse hepcidin by dietary iron and parenterally administered iron dextran: compartmentalization is critical for iron sensing.

    Science.gov (United States)

    Daba, Alina; Gkouvatsos, Konstantinos; Sebastiani, Giada; Pantopoulos, Kostas

    2013-01-01

    The iron regulatory hormone hepcidin responds to both oral and parenteral iron. Here, we hypothesized that the diverse iron trafficking routes may affect the dynamics and kinetics of the hepcidin activation pathway. To address this, C57BL/6 mice were administered an iron-enriched diet or injected i.p. with iron dextran and analyzed over time. After 1 week of dietary loading with carbonyl iron, mice exhibited significant increases in serum iron and transferrin saturation, as well as in hepatic iron, Smad1/5/8 phosphorylation and bone morphogenetic protein 6 (BMP6), and hepcidin mRNAs. Nevertheless, hepcidin expression reached a plateau afterward, possibly due to upregulation of inhibitory Smad7, Id1, and matriptase-2 mRNAs, while hepatic and splenic iron continued to accumulate over 9 weeks. One day following parenteral administration of iron dextran, mice manifested elevated serum and hepatic iron levels and Smad1/5/8 phosphorylation, but no increases in transferrin saturation or BMP6 mRNA. Surprisingly, hepcidin failed to appropriately respond to acute overload with iron dextran, and a delayed (after 5-7 days) hepcidin upregulation correlated with increased transferrin saturation, partial relocation of iron from macrophages to hepatocytes, and induction of BMP6 mRNA. Our data suggest that the physiological hepcidin response is saturable and are consistent with the idea that hepcidin senses exclusively iron compartmentalized within circulating transferrin and/or hepatocytes.

  15. Topographic distribution of brain iron deposition and small cerebrovascular lesions in amyotrophic lateral sclerosis and in frontotemporal lobar degeneration: a post-mortem 7.0-tesla magnetic resonance imaging study with neuropathological correlates.

    Science.gov (United States)

    De Reuck, Jacques; Devos, David; Moreau, Caroline; Auger, Florent; Durieux, Nicolas; Deramecourt, Vincent; Pasquier, Florence; Maurage, Claude-Alain; Cordonnier, Charlotte; Leys, Didier; Bordet, Regis

    2017-12-01

    Amyotrophic lateral sclerosis (ALS) is associated with frontotemporal lobar degeneration (FTLD) in 15% of the cases. A neuropathological continuity between ALS and FTLD-TDP is suspected. The present post-mortem 7.0-tesla magnetic resonance imaging (MRI) study compares the topographic distribution of iron (Fe) deposition and the incidence of small cerebrovascular lesions in ALS and in FTLD brains. Seventy-eight post-mortem brains underwent 7.0-tesla MRI. The patients consisted of 12 with ALS, 38 with FTLD, and 28 controls. Three ALS brains had minor FTLD features. Three coronal sections of a cerebral hemisphere were submitted to T2 and T2* MRI sequences. The amount of Fe deposition in the deep brain structures and the number of small cerebrovascular lesions was determined in ALS and the subtypes of FTLD compared to control brains, with neuropathological correlates. A significant increase of Fe deposition was observed in the claustrum, caudate nucleus, globus pallidus, thalamus, and subthalamic nucleus of the FTLD-FUS and FTLD-TDP groups, while in the ALS one, the Fe increase was only observed in the caudate and the subthalamic nuclei. White matter changes were only significantly more severe in the FTLD compared to those in ALS and in controls brains. Cortical micro-bleeds were increased in the frontal and temporal lobes of FTLD as well as of ALS brains compared to controls. Cortical micro-infarcts were, on the other hand, more frequent in the control compared to the ALS and FTLD groups. The present study supports the assumption of a neuropathological continuity between ALS and FTLD and illustrates the favourable vascular risk profile in these diseases.

  16. Genetic and biochemical markers in patients with Alzheimer's disease support a concerted systemic iron homeostasis dysregulation.

    Science.gov (United States)

    Crespo, Ângela C; Silva, Bruno; Marques, Liliana; Marcelino, Erica; Maruta, Carolina; Costa, Sónia; Timóteo, Angela; Vilares, Arminda; Couto, Frederico Simões; Faustino, Paula; Correia, Ana Paula; Verdelho, Ana; Porto, Graça; Guerreiro, Manuela; Herrero, Ana; Costa, Cristina; de Mendonça, Alexandre; Costa, Luciana; Martins, Madalena

    2014-04-01

    Alzheimer's disease (AD) is the most common form of dementia in the elderly individuals, resulting from a complex interaction between environmental and genetic factors. Impaired brain iron homeostasis has been recognized as an important mechanism underlying the pathogenesis of this disease. Nevertheless, the knowledge gathered so far at the systemic level is clearly insufficient. Herein, we used an integrative approach to study iron metabolism in the periphery, at both genotypic and phenotypic levels, in a sample of 116 patients with AD and 89 healthy control subjects. To assess the potential impact of iron metabolism on the risk of developing AD, genetic analyses were performed along with the evaluation of the iron status profile in peripheral blood by biochemical and gene expression studies. The results obtained showed a significant decrease of serum iron, ferritin, and transferrin concentrations in patients compared with the control subjects. Also, a significant decrease of ferroportin (SLC40A1) and both transferrin receptors TFRC and TFR2 transcripts was found in peripheral blood mononuclear cells from patients. At the genetic level, significant associations with AD were found for single nucleotide polymorphisms in TF, TFR2, ACO1, and SLC40A1 genes. Apolipoprotein E gene, a well-known risk factor for AD, was also found significantly associated with the disease in this study. Taken together, we hypothesize that the alterations on systemic iron status observed in patients could reflect an iron homeostasis dysregulation, particularly in cellular iron efflux. The intracellular iron accumulation would lead to a rise in oxidative damage, contributing to AD pathophysiology. Copyright © 2014 Elsevier Inc. All rights reserved.

  17. Boosting performance in brain-machine interface by classifier-level fusion based on accumulative training models from multi-day data.

    Science.gov (United States)

    Huijuan Yang; Libedinsky, Camilo; Cuntai Guan; Kai Keng Ang; So, Rosa Q

    2017-07-01

    The nonstationarity of neural signal is still an unresolved issue despite the rapid progress made in brain-machine interface (BMI). This paper investigates how to utilize the rich information and dynamics in multi-day data to address the variability in day-to-day signal quality and neural tuning properties. For this purpose, we propose a classifier-level fusion technique to build a robust decoding model by jointly considering the classifier outputs from multiple base-training models using multi-day data collected prior to test day. The data set used in this study consisted of recordings of 8 days from a non-human primate (NHP) during control of a mobile robot using a joystick. Offline analysis demonstrates the superior performance of the proposed method which results in 4.4% and 13.10% improvements in decoding (significant by one-way ANOVA and post hoc t-test) compared with the two baseline methods: 1) concatenating data from multiple days based on common effective channels, and 2) averaging accuracies across all base-training models. These results further validate the effectiveness of proposed method without recalibration of the model.

  18. MYELODYSPLASTIC SYNDROMES AND IRON CHELATION THERAPY

    Directory of Open Access Journals (Sweden)

    Emanuele Angelucci

    2017-03-01

    Full Text Available Over recent decades we have been fortunate to witness the advent of new technologies and of an expanded knowledge and application of chelation therapies to the benefit of patients with iron overload. However, extrapolation of learnings from thalassemia to the myelodysplastic syndromes (MDS has resulted in a fragmented and uncoordinated clinical evidence base. We’re therefore forced to change our understanding of MDS, looking with other eyes to observational studies that inform us about the relationship between iron and tissue damage in these subjects. The available evidence suggests that iron accumulation is prognostically significant in MDS, but levels of accumulation historically associated with organ damage (based on data generated in the thalassemias are infrequent. Emerging experimental data have provided some insight into this paradox, as our understanding of iron-induced tissue damage has evolved from a process of progressive bulking of organs through high-volumes iron deposition, to one of ‘toxic’ damage inflicted through multiple cellular pathways. Damage from iron may therefore occur prior to reaching reference thresholds, and similarly, chelation may be of benefit before overt iron overload is seen. In this review, we revisit the science and clinical evidence for iron overload in MDS to better characterise the iron overload phenotype in these patients, which is distinct from the classical transfusional and non-transfusional iron overload syndrome. We hope this will provide a conceptual framework to better understand the complex associations between anemia, iron and clinical outcomes, to accelerate progress in this area.

  19. Metal ion toxins and brain aquaporin-4 expression: an overview

    Directory of Open Access Journals (Sweden)

    Adriana eXimenes-Da-Silva

    2016-06-01

    Full Text Available Metal ions such as iron, zinc, and manganese are essential to metabolic functions, protein synthesis, neurotransmission, and antioxidant neuroprotective mechanisms. Conversely, non-essential metals such as mercury and lead are sources of human intoxication due to occupational activities or environmental contamination. Essential or non-essential metal accumulation in the central nervous system (CNS results in changes in blood-brain barrier (BBB permeability, as well as triggering microglia activation and astrocyte reactivity and changing water transport through the cells, which could result in brain swelling. Aquaporin-4 is the main water channel in the CNS, is expressed in astrocyte foot processes in brain capillaries and along the circumventricular epithelium in the ventricles, and has important physiological functions in maintaining brain osmotic homeostasis and supporting brain excitability through regulation of the extracellular space. Some evidence has pointed to a role of AQP4 during metal intoxication in the brain, where it may act in a dual form as a neuroprotector or a mediator of the development of oxidative stress in neurons and astrocytes, resulting in brain swelling and neuronal damage. This mini-review presents the way some metal ions affect changes in AQP4 expression in the CNS and discuss the ways in which water transport in brain cells can be involved in brain damage.

  20. Iron, zinc, and manganese distribution in mature soybean seeds

    DEFF Research Database (Denmark)

    Cvitanich, Cristina; Przybyłowicz, Wojciech J; Mesjasz-Przybyłowicz, Jolanta

    2009-01-01

    to reveal the distribution of iron, zinc, manganese and phosphorus within soybean seeds. We show that high concentrations of iron accumulate in the seed coats of mature soybean seeds. This iron accounted for 20 to 40% of the total seed iron. Furthermore, manganese and iron accumulated in close proximity...... to each other in the provascular tissue of the soybean radicle. No regions with increased accumulation of iron, zinc, or manganese were observed in the cotyledons. The concentrations of both phosphorus and zinc were higher in the radicle compared to the cotyledons, and zinc accumulated primarily near...... the radicle tip. Our study provides a thorough description of the distribution of important micronutrients within the mature soybean seed....

  1. Iron refractory iron deficiency anemia

    Science.gov (United States)

    De Falco, Luigia; Sanchez, Mayka; Silvestri, Laura; Kannengiesser, Caroline; Muckenthaler, Martina U.; Iolascon, Achille; Gouya, Laurent; Camaschella, Clara; Beaumont, Carole

    2013-01-01

    Iron refractory iron deficiency anemia is a hereditary recessive anemia due to a defect in the TMPRSS6 gene encoding Matriptase-2. This protein is a transmembrane serine protease that plays an essential role in down-regulating hepcidin, the key regulator of iron homeostasis. Hallmarks of this disease are microcytic hypochromic anemia, low transferrin saturation and normal/high serum hepcidin values. The anemia appears in the post-natal period, although in some cases it is only diagnosed in adulthood. The disease is refractory to oral iron treatment but shows a slow response to intravenous iron injections and partial correction of the anemia. To date, 40 different Matriptase-2 mutations have been reported, affecting all the functional domains of the large ectodomain of the protein. In vitro experiments on transfected cells suggest that Matriptase-2 cleaves Hemojuvelin, a major regulator of hepcidin expression and that this function is altered in this genetic form of anemia. In contrast to the low/undetectable hepcidin levels observed in acquired iron deficiency, in patients with Matriptase-2 deficiency, serum hepcidin is inappropriately high for the low iron status and accounts for the absent/delayed response to oral iron treatment. A challenge for the clinicians and pediatricians is the recognition of the disorder among iron deficiency and other microcytic anemias commonly found in pediatric patients. The current treatment of iron refractory iron deficiency anemia is based on parenteral iron administration; in the future, manipulation of the hepcidin pathway with the aim of suppressing it might become an alternative therapeutic approach. PMID:23729726

  2. Iron metabolism in BeWo chorion carcinoma cells. Transferrin-mediated uptake and release of iron

    NARCIS (Netherlands)

    van der Ende, A.; du Maine, A.; Simmons, C. F.; Schwartz, A. L.; Strous, G. J.

    1987-01-01

    Growing human choriocarcinoma BeWo b24 cells contain 1.5 X 10(6) functional cell surface transferrin binding sites and 2.0 X 10(6) intracellular binding sites. These cells rapidly accumulate iron at a rate of 360,000 iron atoms/min/cell. During iron uptake the transferrin and its receptor recycle at

  3. Thyroid Hormone-Dependent Formation of a Subcortical Band Heterotopia (SBH) in the Neonatal Brain is not Exacerbated Under Conditions of Low Dietary Iron

    Science.gov (United States)

    Thyroid hormones (TH) are critical for brain development. Modest TH insufficiency in pregnant rats induced by propylthiouracil (PTU) results in formation of a structural abnormality, a subcortical band heterotopia (SBH), in brains of offspring. PTU reduces TH by inhibiting the s...

  4. Cristobalite and Hematite Particles in Human Brain.

    Science.gov (United States)

    Kopani, Martin; Kopaniova, A; Trnka, M; Caplovicova, M; Rychly, B; Jakubovsky, J

    2016-11-01

    Foreign substances get into the internal environment of living bodies and accumulate in various organs. Cristobalite and hematite particles in the glial cells of pons cerebri of human brain with diagnosis of Behhet disease with scanning electron microscopy (SEM), energy-dispersive microanalysis (EDX), and transmission electron microscopy (TEM) with diffraction were identified. SEM with EDX revealed the matter of irregular micrometer-sized particles sometimes forming polyhedrons with fibrilar or stratified structure. It was found in some particles Ti, Fe, and Zn. Some particles contained Cu. TEM and electron diffraction showed particles of cristobalite and hematite. The presence of the particles can be a result of environmental effect, disruption of normal metabolism, and transformation of physiologically iron-ferrihydrite into more stable form-hematite. From the size of particles can be drawn the long-term accumulation of elements in glial cells.

  5. Cellular Imaging at 1.5 T: Detecting Cells in Neuroinflammation using Active Labeling with Superparamagnetic Iron Oxide

    Directory of Open Access Journals (Sweden)

    Ayman J. Oweida

    2004-04-01

    Full Text Available The ability to visualize cell infiltration in experimental autoimmune encephalomyelitis (EAE, a well-known animal model for multiple sclerosis in humans, was investigated using a clinical 1.5-T magnetic resonance imaging (MRI scanner, a custom-built, high-strength gradient coil insert, a 3-D fast imaging employing steady-state acquisition (FIESTA imaging sequence and a superparamagnetic iron oxide (SPIO contrast agent. An “active labeling” approach was used with SPIO administered intravenously during inflammation in EAE. Our results show that small, discrete regions of signal void corresponding to iron accumulation in EAE brain can be detected using FIESTA at 1.5 T. This work provides early evidence that cellular abnormalities that are the basis of diseases can be probed using cellular MRI and supports our earlier work which indicates that tracking of iron-labeled cells will be possible using clinical MR scanners.

  6. Cast irons

    CERN Document Server

    1996-01-01

    Cast iron offers the design engineer a low-cost, high-strength material that can be easily melted and poured into a wide variety of useful, and sometimes complex, shapes. This latest handbook from ASM covers the entire spectrum of one of the most widely used and versatile of all engineered materials. The reader will find the basic, but vital, information on metallurgy, solidification characteristics, and properties. Extensive reviews are presented on the low-alloy gray, ductile, compacted graphite, and malleable irons. New and expanded material has been added covering high-alloy white irons used for abrasion resistance and high-alloy graphitic irons for heat and corrosion resistance. Also discussed are melting furnaces and foundry practices such as melting, inoculation, alloying, pouring, gating and rising, and molding. Heat treating practices including stress relieving, annealing, normalizing, hardening and tempering, autempering (of ductile irons), and surface-hardening treatments are covered, too. ASM Spec...

  7. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... your body doesn't have enough iron to build healthy red blood cells. Without enough iron, your ... Supplements Iron You may need iron supplements to build up your iron levels as quickly as possible. ...

  8. Nitric oxide and changes of iron metabolism in exercise.

    Science.gov (United States)

    Qian, Zhong Ming

    2002-11-01

    Accumulated data imply that exercise itself might not lead to a true iron deficiency or 'sport anaemia' in a healthy athlete who has adequate iron intake. The higher prevalence of iron deficiency anaemia in younger female athletes might be not due to exercise itself, but probably results from dietary choices, inadequate iron intake and menstruation. These factors can also induce iron deficiency or anaemia in the general population. However, exercise does affect iron metabolism, leading to low or sub-optimal iron status. The underlying mechanism is unknown. In this review, recent advances in the study of the effect of exercise on iron metabolism and nitric oxide, and the relationship between nitric oxide and iron status in exercise are discussed. A hypothesis that increased production of nitric oxide might contribute to sub-optimal iron status in exercise is proposed.

  9. Thyroid Hormone-Dependent Formation of a Subcortical Band Heterotopia (SBH) in the Neonatal Brain is not Exacerbated Under Conditions of Low Dietary Iron (FeD)

    Science.gov (United States)

    Although the critical role of thyroid hormone (TH) in brain development is well established - severe deficiency producing significant neurological dysfunction - there is a paucity of data on neurological impairments that accompany modest degrees of TH disruption. Quantitative m...

  10. Biochemistry of the normal dura mater of the human brain determination of water, sodium, potassium, calcium, phosphorus, magnesium, copper, iron, sulfur and nitrogen contents

    Directory of Open Access Journals (Sweden)

    Horacio M. Canelas

    1969-06-01

    Full Text Available The concentrations of water, sodium, potassium, calcium, phosphorus, magnesium, copper, iron, sulfur, and nitrogen were determined in samples of apparently normal dura mater removed from 18 subjects recently dead by craniocerebral trauma. The average concentrations expressed in dry weight were: water 79.55 g/100 g ± 2.52; sodium 1.63 mequiv/100 g ±0.27; potassium 3.68 mequiv/100 g ± 0.66; calcium 119.84 mg/100 g ± 107.40; phosphorus 68.2 mg/100 g ± 34.5; magnesium 0.61 mequiv/100 g ± 0.37; copper 249.8 /xg/100 g ± 109.4; iron 0.82 mg/100 g ± 0.28; sulfur 490.7 mg/100 g ± 22.5; nitrogen 3.33 g/100 g ± 0.17.

  11. Slow expansion of multiple sclerosis iron rim lesions: pathology and 7 T magnetic resonance imaging.

    Science.gov (United States)

    Dal-Bianco, Assunta; Grabner, Günther; Kronnerwetter, Claudia; Weber, Michael; Höftberger, Romana; Berger, Thomas; Auff, Eduard; Leutmezer, Fritz; Trattnig, Siegfried; Lassmann, Hans; Bagnato, Francesca; Hametner, Simon

    2017-01-01

    In multiple sclerosis (MS), iron accumulates inside activated microglia/macrophages at edges of some chronic demyelinated lesions, forming rims. In susceptibility-based magnetic resonance imaging at 7 T, iron-laden microglia/macrophages induce a rim of decreased signal at lesion edges and have been associated with slowly expanding lesions. We aimed to determine (1) what lesion types and stages are associated with iron accumulation at their edges, (2) what cells at the lesion edges accumulate iron and what is their activation status, (3) how reliably can iron accumulation at the lesion edge be detected by 7 T magnetic resonance imaging (MRI), and (4) if lesions with rims enlarge over time in vivo, when compared to lesions without rims. Double-hemispheric brain sections of 28 MS cases were stained for iron, myelin, and microglia/macrophages. Prior to histology, 4 of these 28 cases were imaged at 7 T using post-mortem susceptibility-weighted imaging. In vivo, seven MS patients underwent annual neurological examinations and 7 T MRI for 3.5 years, using a fluid attenuated inversion recovery/susceptibility-weighted imaging fusion sequence. Pathologically, we found iron rims around slowly expanding and some inactive lesions but hardly around remyelinated shadow plaques. Iron in rims was mainly present in microglia/macrophages with a pro-inflammatory activation status, but only very rarely in astrocytes. Histological validation of post-mortem susceptibility-weighted imaging revealed a quantitative threshold of iron-laden microglia when a rim was visible. Slowly expanding lesions significantly exceeded this threshold, when compared with inactive lesions (p = 0.003). We show for the first time that rim lesions significantly expanded in vivo after 3.5 years, compared to lesions without rims (p = 0.003). Thus, slow expansion of MS lesions with rims, which reflects chronic lesion activity, may, in the future, become an MRI marker for disease activity in MS.

  12. Seasonal Arsenic Accumulation in Stream Sediments at a Groundwater Discharge Zone

    DEFF Research Database (Denmark)

    MacKay, Allison A.; Gan, Ping; Yu, Ran

    2014-01-01

    Seasonal changes in arsenic and iron accumulation rates were examined in the sediments of a brook that receives groundwater discharges of arsenic and reduced iron. Clean glass bead columns were deployed in sediments for known periods over the annual hydrologic cycle to monitor changes in arsenic......(As)/mg(Fe)) of unreacted iron oxide solids. The flooded spring (March-June) with high surface water flows showed the lowest arsenic and iron accumulation rates in the sediments. Comparisons of accumulation rates across a shoreline transect were consistent with greater rates at regions exposed above surface water levels...

  13. Iron Test

    Science.gov (United States)

    ... Pregnancy hCG Tumor Marker HDL Cholesterol Heavy Metals Helicobacter pylori Testing Hematocrit Hemoglobin Hemoglobin A1c Hemoglobinopathy Evaluation ... not enough iron is taken in from the diet, blood levels will drop; thus, over time, the ...

  14. Iron, anemia and hepcidin in malaria.

    Science.gov (United States)

    Spottiswoode, Natasha; Duffy, Patrick E; Drakesmith, Hal

    2014-01-01

    Malaria and iron have a complex but important relationship. Plasmodium proliferation requires iron, both during the clinically silent liver stage of growth and in the disease-associated phase of erythrocyte infection. Precisely how the protozoan acquires its iron from its mammalian host remains unclear, but iron chelators can inhibit pathogen growth in vitro and in animal models. In humans, iron deficiency appears to protect against severe malaria, while iron supplementation increases risks of infection and disease. Malaria itself causes profound disturbances in physiological iron distribution and utilization, through mechanisms that include hemolysis, release of heme, dyserythropoiesis, anemia, deposition of iron in macrophages, and inhibition of dietary iron absorption. These effects have significant consequences. Malarial anemia is a major global health problem, especially in children, that remains incompletely understood and is not straightforward to treat. Furthermore, the changes in iron metabolism during a malaria infection may modulate susceptibility to co-infections. The release of heme and accumulation of iron in granulocytes may explain increased vulnerability to non-typhoidal Salmonella during malaria. The redistribution of iron away from hepatocytes and into macrophages may confer host resistance to superinfection, whereby blood-stage parasitemia prevents the development of a second liver-stage Plasmodium infection in the same organism. Key to understanding the pathophysiology of iron metabolism in malaria is the activity of the iron regulatory hormone hepcidin. Hepcidin is upregulated during blood-stage parasitemia and likely mediates much of the iron redistribution that accompanies disease. Understanding the regulation and role of hepcidin may offer new opportunities to combat malaria and formulate better approaches to treat anemia in the developing world.

  15. Iron, anemia and hepcidin in malaria

    Directory of Open Access Journals (Sweden)

    Natasha eSpottiswoode

    2014-05-01

    Full Text Available Malaria and iron have a complex but important relationship. Plasmodium proliferation requires iron, both during the clinically silent liver stage of growth and in the disease-associated phase of erythrocyte infection. Precisely how the protozoan acquires its iron from its mammalian host remains unclear, but iron chelators can inhibit pathogen growth in vitro and in animal models. In humans, iron deficiency appears to protect against severe malaria, while iron supplementation increases risks of infection and disease. Malaria itself causes profound disturbances in physiological iron distribution and utilization, through mechanisms that include hemolysis, release of heme, dyserythropoiesis, anemia, deposition of iron in macrophages, and inhibition of dietary iron absorption. These effects have significant consequences. Malarial anemia is a major global health problem, especially in children, that remains incompletely understood and is not straightforward to treat. Furthermore, the changes in iron metabolism during a malaria infection may modulate susceptibility to coinfections. The release of heme and accumulation of iron in granulocytes may explain increased vulnerability to non-typhoidal Salmonella during malaria. The redistribution of iron away from hepatocytes and into macrophages may confer host resistance to superinfection, whereby blood-stage parasitemia prevents the development of a second liver-stage Plasmodium infection in the same organism. Key to understanding the pathophysiology of iron metabolism in malaria is the activity of the iron regulatory hormone hepcidin. Hepcidin is upregulated during blood-stage parasitemia and likely mediates much of the iron redistribution that accompanies disease. Understanding the regulation and role of hepcidin may offer new opportunities to combat malaria and formulate better approaches to treat anemia in the developing world.

  16. Iron biomineralization by anaerobic neutrophilic iron-oxidizing bacteria

    Science.gov (United States)

    Miot, Jennyfer; Benzerara, Karim; Morin, Guillaume; Kappler, Andreas; Bernard, Sylvain; Obst, Martin; Férard, Céline; Skouri-Panet, Fériel; Guigner, Jean-Michel; Posth, Nicole; Galvez, Matthieu; Brown, Gordon E., Jr.; Guyot, François

    2009-02-01

    Minerals formed by bio-oxidation of ferrous iron (Fe(II)) at neutral pH, their association with bacterial ultrastructures as well as their impact on the metabolism of iron-oxidizing bacteria remain poorly understood. Here, we investigated iron biomineralization by the anaerobic nitrate-dependent iron-oxidizing bacterium Acidovorax sp. strain BoFeN1 in the presence of dissolved Fe(II) using electron microscopy and Scanning Transmission X-ray Microscopy (STXM). All detected minerals consisted mainly of amorphous iron phosphates, but based on their morphology and localization, three types of precipitates could be discriminated: (1) mineralized filaments at distance from the cells, (2) globules of 100 ± 25 nm in diameter, at the cell surface and (3) a 40-nm thick mineralized layer within the periplasm. All of those phases were shown to be intimately associated with organic molecules. Periplasmic encrustation was accompanied by an accumulation of protein moieties. In the same way, exopolysaccharides were associated with the extracellular mineralized filaments. The evolution of cell encrustation was followed by TEM over the time course of a culture: cell encrustation proceeded progressively, with rapid precipitation in the periplasm (in a few tens of minutes), followed by the formation of surface-bound globules. Moreover, we frequently observed an asymmetric mineral thickening at the cell poles. In parallel, the evolution of iron oxidation was quantified by STXM: iron both contained in the bacteria and in the extracellular precipitates reached complete oxidation within 6 days. While a progressive oxidation of Fe in the bacteria and in the medium could be observed, spatial redox (oxido-reduction state) heterogeneities were detected at the cell poles and in the extracellular precipitates after 1 day. All these findings provide new information to further the understanding of molecular processes involved in iron biomineralization by anaerobic iron-oxidizing bacteria and

  17. Perinatal iron deficiency and neurocognitive development

    Directory of Open Access Journals (Sweden)

    Emily Clare Radlowski

    2013-09-01

    Full Text Available Iron deficiency is the most common form of nutrient deficiency worldwide. It is highly prevalent due to the limited availability of high quality food in developing countries, and poor dietary habits in industrialized countries. According to the World Health Organization, it affects nearly 2 billion people and up to 50% of women who are pregnant. Maternal anemia during pregnancy is especially burdensome to healthy neurodevelopment in the fetus because iron is needed for proper neurogenesis, development, and myelination. Maternal anemia also increases the risk of low birth weight, either due to premature birth or fetal growth restriction, which is associated with delayed neurocognitive development and even psychiatric illness. As rapid neurodevelopment continues after birth infants that received sufficient iron in utero, but that receive a low iron diet after 6 months of age, also show deficits in neurocognitive development, including impairments in learning and memory. Unfortunately, the neurocognitive complications of iron deficiency during critical pre- and postnatal periods of brain development are difficult to remedy, persisting into adulthood. Thus, preventing iron deficiency in the pre- and postnatal periods is critical as is devising new means to recapture cognitive function in individuals who experienced early iron deficiency. This review will discuss the prevalence of pre- and postnatal iron deficiency, the mechanism, and effects of iron deficiency on brain and cognitive development.

  18. Iron Chelation Nanoparticles with Delayed Saturation as an Effective Therapy for Parkinson Disease.

    Science.gov (United States)

    Wang, Nan; Jin, Xin; Guo, Dongbo; Tong, Gangsheng; Zhu, Xinyuan

    2017-02-13

    Iron accumulation in substantia nigra pars compacta (SNpc) has been proved to be a prominent pathophysiological feature of Parkinson's diseases (PD), which can induce the death of dopaminergic (DA) neurons, up-regulation of reactive oxygen species (ROS), and further loss of motor control. In recent years, iron chelation therapy has been demonstrated to be an effective treatment for PD, which has shown significant improvements in clinical trials. However, the current iron chelators are suboptimal due to their short circulation time, side effects, and lack of proper protection from chelation with ions in blood circulation. In this work, we designed and constructed iron chelation therapeutic nanoparticles protected by a zwitterionic poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC) to delay the saturation of iron chelators in blood circulation and prolong the in vivo lifetime, with HIV-1 trans-activating transcriptor (TAT) served as a shuttle to enhance the blood-brain barrier (BBB) permeability. We explored and investigated whether the Parkinsonian neurodegeneration and the corresponding symptoms in behaviors and physiologies could be prevented or reversed both in vitro and in vivo. The results demonstrated that iron chelator loaded therapeutic nanoparticles could reverse functional deficits in Parkinsonian mice not only physiologically but also behaviorally. On the contrary, both untreated PD mice and non-TAT anchored nanoparticle treated PD mice showed similar loss in DA neurons and difficulties in behaviors. Therefore, with protection of zwitterionic polymer and prolonged in vivo lifetime, iron chelator loaded nanoparticles with delayed saturation provide a PD phenotype reversion therapy and significantly improve the living quality of the Parkinsonian mice.

  19. Iron biofortification and homeostasis in transgenic cassava roots expressing an algal iron assimilatory protein, FEA1

    Directory of Open Access Journals (Sweden)

    Uzoma eIhemere

    2012-09-01

    Full Text Available We have engineered the starchy root crop cassava (Manihot esculenta to express the Chlamydomonas reinhardtii iron assimilatory protein, FEA1, in roots to enhance its nutritional qualities. Iron levels in mature cassava storage roots were increased from 10 to 36 ppm in the highest iron accumulating transgenic lines. These iron levels are sufficient to meet the minimum daily requirement for iron in a 500 gm meal. Significantly, the expression of the FEA1 protein did not alter iron levels in leaves. Transgenic plants also had normal levels of zinc in leaves and roots consistent with the specific uptake of iron mediated by the FEA1 protein. Relative to wild-type plants, FEA1 expressing plants had reduced Fe(III chelate reductase activity and gene expression levels consistent with the more efficient uptake of iron in FEA1 transgenic plants. We also show that genes involved in iron homeostasis in cassava have altered tissue-specific patterns of expression in transgenic plants. Steady state transcript levels of the metal-chelate transporter MeYSL1, and the iron storage proteins, MeFER2 and MeFER6, were elevated in various tissues of FEA1 transgenic plants compared to wild-type plants. These results suggest that these gene products play a role in iron translocation and homeostasis in FEA1 transgenic cassava plants. These results are discussed in terms of enhanced strategies for the iron biofortification of plants.

  20. Iron overload in very low birth weight infants: Serum Ferritin and adverse outcomes

    LENUS (Irish Health Repository)

    Barrett, M

    2011-11-01

    Adequate iron isessential for growth and haematpoiesis. Oral iron supplementation is the standard of care in VLBW infants. Post mortem evidence has confirmed significant iron overload. Excessive free iron has been associated with free radical formation and brain injury in term infants.

  1. NCOA4 Deficiency Impairs Systemic Iron Homeostasis

    Directory of Open Access Journals (Sweden)

    Roberto Bellelli

    2016-01-01

    Full Text Available The cargo receptor NCOA4 mediates autophagic ferritin degradation. Here we show that NCOA4 deficiency in a knockout mouse model causes iron accumulation in the liver and spleen, increased levels of transferrin saturation, serum ferritin, and liver hepcidin, and decreased levels of duodenal ferroportin. Despite signs of iron overload, NCOA4-null mice had mild microcytic hypochromic anemia. Under an iron-deprived diet (2–3 mg/kg, mice failed to release iron from ferritin storage and developed severe microcytic hypochromic anemia and ineffective erythropoiesis associated with increased erythropoietin levels. When fed an iron-enriched diet (2 g/kg, mice died prematurely and showed signs of liver damage. Ferritin accumulated in primary embryonic fibroblasts from NCOA4-null mice consequent to impaired autophagic targeting. Adoptive expression of the NCOA4 COOH terminus (aa 239–614 restored this function. In conclusion, NCOA4 prevents iron accumulation and ensures efficient erythropoiesis, playing a central role in balancing iron levels in vivo.

  2. NCOA4 Deficiency Impairs Systemic Iron Homeostasis.

    Science.gov (United States)

    Bellelli, Roberto; Federico, Giorgia; Matte', Alessandro; Colecchia, David; Iolascon, Achille; Chiariello, Mario; Santoro, Massimo; De Franceschi, Lucia; Carlomagno, Francesca

    2016-01-26

    The cargo receptor NCOA4 mediates autophagic ferritin degradation. Here we show that NCOA4 deficiency in a knockout mouse model causes iron accumulation in the liver and spleen, increased levels of transferrin saturation, serum ferritin, and liver hepcidin, and decreased levels of duodenal ferroportin. Despite signs of iron overload, NCOA4-null mice had mild microcytic hypochromic anemia. Under an iron-deprived diet (2-3 mg/kg), mice failed to release iron from ferritin storage and developed severe microcytic hypochromic anemia and ineffective erythropoiesis associated with increased erythropoietin levels. When fed an iron-enriched diet (2 g/kg), mice died prematurely and showed signs of liver damage. Ferritin accumulated in primary embryonic fibroblasts from NCOA4-null mice consequent to impaired autophagic targeting. Adoptive expression of the NCOA4 COOH terminus (aa 239-614) restored this function. In conclusion, NCOA4 prevents iron accumulation and ensures efficient erythropoiesis, playing a central role in balancing iron levels in vivo. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  3. Iron enriched yeast biomass--a promising mineral feed supplement.

    Science.gov (United States)

    Pas, Maja; Piskur, Barbara; Sustaric, Matevz; Raspor, Peter

    2007-05-01

    Yeast biomass enriched with iron could represent a new and safer solution for prevention from anaemia development. Such an iron source is less toxic and has better absorbability in organisms. The purpose of our research was the determination of the most suitable iron source in the cultivation medium for the yeast Saccharomyces cerevisiae, regarding good growth and iron accumulation in cells. Iron(III) citrate, iron(III) chloride, iron(III) nitrate and Fe-EDTA complex were used. The uptake of the chosen iron compound, Fe(III) citrate, by the yeasts Candida intermedia and Kluyveromyces marxianus was also investigated. Different growth behaviour of the three yeast strains in the presence of Fe(III) citrate was observed. The highest amounts of accumulated iron in S. cerevisiae, C. intermedia and K. marxianus biomass were about 13, 20 and 34mgFeg(-1)dry wt., respectively. To optimise the accumulation of iron in K. marxianus and to characterise iron enriched yeast biomass, further experiments are needed.

  4. Pica as a manifestation of iron deficiency.

    Science.gov (United States)

    Borgna-Pignatti, Caterina; Zanella, Sara

    2016-11-01

    Pica is the compulsive eating of non-nutritive substances. It is often associated with iron deficiency but its pathophysiology is unknown. Areas covered: We searched the literature using the keywords listed below. Our aim was to describe the phenomenon in its various aspects, to touch briefly on the historical and cultural background, and to examine in more detail the studies that tried to analyze the relative roles of iron deficiency and pica. Expert commentary: Pica is an intriguing symptom known for centuries. Pregnant women and preadolescents are at the highest risk of pica. Iron absorption is reduced in the presence of non-nutritive substances. Iron therapy usually cures the pica behavior. There are different forms of pica, one caused directly by iron deficiency probably due to the lack of iron in some areas of the brain and one more culturally driven and including mostly geophagy.

  5. Obesity Promotes Alterations in Iron Recycling

    Directory of Open Access Journals (Sweden)

    Marta Citelli

    2015-01-01

    Full Text Available Hepcidin is a key hormone that induces the degradation of ferroportin (FPN, a protein that exports iron from reticuloendothelial macrophages and enterocytes. The aim of the present study was to experimentally evaluate if the obesity induced by a high-fat diet (HFD modifies the expression of FPN in macrophages and enterocytes, thus altering the iron bioavailability. In order to directly examine changes associated with iron metabolism in vivo, C57BL/6J mice were fed either a control or a HFD. Serum leptin levels were evaluated. The hepcidin, divalent metal transporter-1 (DMT1, FPN and ferritin genes were analyzed by real-time polymerase chain reaction. The amount of iron present in both the liver and spleen was determined by flame atomic absorption spectrometry. Ferroportin localization within reticuloendothelial macrophages was observed by immunofluorescence microscopy. Obese animals were found to exhibit increased hepcidin gene expression, while iron accumulated in the spleen and liver. They also exhibited changes in the sublocation of splenic cellular FPN and a reduction in the FPN expression in the liver and the spleen, while no changes were observed in enterocytes. Possible explanations for the increased hepcidin expression observed in HFD animals may include: increased leptin levels, the liver iron accumulation or endoplasmic reticulum (ER stress. Together, the results indicated that obesity promotes changes in iron bioavailability, since it altered the iron recycling function.

  6. Iron Dextran Injection

    Science.gov (United States)

    Iron dextran injection is used to treat iron-deficiency anemia (a lower than normal number of red blood ... be treated with iron supplements taken by mouth. Iron dextran injection is in a class of medications called ...

  7. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... re more likely to develop iron-deficiency anemia. Vegetarian diets can provide enough iron if you eat ... which are the best sources of iron. However, vegetarian diets can provide enough iron if you eat ...

  8. Iron-Deficiency Anemia

    Science.gov (United States)

    ... re more likely to develop iron-deficiency anemia. Vegetarian diets can provide enough iron if you eat ... which are the best sources of iron. However, vegetarian diets can provide enough iron if you eat ...

  9. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... can provide enough iron if you eat the right foods. For example, good nonmeat sources of iron ... can provide enough iron if you eat the right foods. For example, good nonmeat sources of iron ...

  10. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... of iron include iron-fortified breads and cereals, beans, tofu, dried fruits, and spinach and other dark ... of iron include iron-fortified breads and cereals, beans, tofu, dried fruits, and spinach and other dark ...

  11. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... enough iron, your body starts using the iron it has stored. Soon, the stored iron gets used ... fewer red blood cells. The red blood cells it does make have less hemoglobin than normal. Iron- ...

  12. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... good nonmeat sources of iron include iron-fortified breads and cereals, beans, tofu, dried fruits, and spinach ... good nonmeat sources of iron include iron-fortified breads and cereals, beans, tofu, dried fruits, and spinach ...

  13. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... The best sources of iron are meat, poultry, fish, and iron-fortified foods (foods that have iron ... you: Follow a diet that excludes meat and fish, which are the best sources of iron. However, ...

  14. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... sources of iron include iron-fortified breads and cereals, beans, tofu, dried fruits, and spinach and other ... sources of iron include iron-fortified breads and cereals, beans, tofu, dried fruits, and spinach and other ...

  15. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... drawings also can cause iron-deficiency anemia. Poor Diet The best sources of iron are meat, poultry, ... more likely to develop iron-deficiency anemia. Vegetarian diets can provide enough iron if you eat the ...

  16. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... iron-deficiency anemia may require treatment in a hospital, blood transfusions , iron injections, or intravenous iron therapy. ... Treatment may need to be done in a hospital. The goals of treating iron-deficiency anemia are ...

  17. Ferrous iron content of intravenous iron formulations

    OpenAIRE

    Gupta, Ajay; Pratt, Raymond D; Crumbliss, Alvin L.

    2016-01-01

    The observed biological differences in safety and efficacy of intravenous (IV) iron formulations are attributable to physicochemical differences. In addition to differences in carbohydrate shell, polarographic signatures due to ferric iron [Fe(III)] and ferrous iron [Fe(II)] differ among IV iron formulations. Intravenous iron contains Fe(II) and releases labile iron in the circulation. Fe(II) generates toxic free radicals and reactive oxygen species and binds to bacterial siderophores and oth...

  18. Iron deficiency

    DEFF Research Database (Denmark)

    Schou, Morten; Bosselmann, Helle; Gaborit, Freja

    2015-01-01

    BACKGROUND: Both iron deficiency (ID) and cardiovascular biomarkers are associated with a poor outcome in heart failure (HF). The relationship between different cardiovascular biomarkers and ID is unknown, and the true prevalence of ID in an outpatient HF clinic is probably overlooked. OBJECTIVES.......043). CONCLUSION: ID is frequent in an outpatient HF clinic. ID is not associated with cardiovascular biomarkers after adjustment for traditional confounders. Inflammation, but not neurohormonal activation is associated with ID in systolic HF. Further studies are needed to understand iron metabolism in elderly HF...

  19. Iron importers Zip8 and Zip14 are expressed in retina and regulated by retinal iron levels.

    Science.gov (United States)

    Sterling, Jacob; Guttha, Samyuktha; Song, Ying; Song, Delu; Hadziahmetovic, Majda; Dunaief, Joshua L

    2017-02-01

    Intracellular retinal iron accumulation has been implicated in the pathogenesis of age-related macular degeneration (AMD), the leading cause of irreversible blindness among individuals over the age of 50. Ceruloplasmin/hephaestin double knockout mice (Cp/Heph DKO) and hepcidin knockout mice (Hepc KO) accumulate retinal iron and model some features of AMD. Two canonical pathways govern cellular iron import - transferrin-bound iron import and non-transferrin bound iron import. In Cp/Heph DKO and Hepc KO iron-loaded retinas, transferrin-bound iron import is downregulated. Despite this effort to reduce cellular iron burden, iron continues to accumulate in these retinas in an age-dependent manner. Quantitative RT-PCR and Western analysis were used to quantify the expression of three ferrous iron importers, Dmt1, Zip8, and Zip14, in wild-type (Wt), Cp/Heph DKO, and Hepc KO retinas. Zip8 and Zip14 protein levels were analyzed using Western analysis in mice injected intravitreally with either apo- or holo-transferrin to elucidate one possible mechanism of Zip14 regulation in the retina. Both zip8 and zip14 were expressed in the mouse retina. Paradoxically, protein levels of non-transferrin bound iron importers were upregulated in both Cp/Heph DKO and Hepc KO retinas. Intravitreal holo-transferrin injection decreased Zip 14 protein levels. These data indicate that Zip8 and Zip14 may take up increasing amounts of non-transferrin bound iron in these two mouse models of retinal iron accumulation. Their upregulation in these already iron-loaded retinas suggests a vicious cycle leading to toxicity. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Iron status as a covariate in methylmercury-associated neurotoxicity risk

    DEFF Research Database (Denmark)

    Fonseca, Márlon de Freitas; De Souza Hacon, Sandra; Grandjean, Philippe

    2014-01-01

    Intrauterine methylmercury exposure and prenatal iron deficiency negatively affect offspring's brain development. Since fish is a major source of both methylmercury and iron, occurrence of negative confounding may affect the interpretation of studies concerning cognition. We assessed relationships...

  1. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... have enough iron stored in your body to make up for the lost iron, you'll develop iron- ... by mouth. This therapy also is given to people who need immediate treatment for iron-deficiency ... have iron-deficiency anemia, get ongoing care to make sure your iron levels are improving. At your ...

  2. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... hospital, blood transfusions , iron injections, or intravenous iron therapy. Causes Not having enough iron in your body causes iron-deficiency anemia. Lack of iron usually is due to blood loss, poor diet, or an inability to absorb enough iron from ...

  3. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... can provide enough iron if you eat the right foods. For example, good nonmeat sources of iron include iron-fortified breads and cereals, ... can provide enough iron if you eat the right foods. For example, good nonmeat sources of iron include iron-fortified breads and cereals, ...

  4. Iron in haemoglobinopathies and rare anaemias

    Directory of Open Access Journals (Sweden)

    John Porter

    2014-12-01

    Full Text Available Iron overload in haemoglobinopathies and rare anaemias may develop from increased iron absorption secondary to hepcidin suppression, and/or from repeated blood transfusions. While the accumulation of body iron load from blood transfusion is inevitable and predictable from the variable rates of transfusion in the different conditions, there are some important differences in the distribution of iron overload and its consequences between these. Transfusion-dependent thalassaemia (TDT is the best described condition in which transfusional overload occurs. Initially iron loads into macrophages, subsquently hepatocytes, and then the endocrine system including the anterior pituiatry and finally the myocardium. The propensity to extrahepatic iron spread increases with rapid transfusion and with inadequate chelation therapy but there is considerable interpatient and interpopulation variability in this tendency. The conduits though which iron is delivered to tissues is through non transferrin iron species (NTBI which are taken into liver, endocrine tissues and myocardium through L-type calcium channells and possibly through other channells. Recent work by the MSCIO group1 suggests that levels of NTBI are determined by three mechanisms: i increasing with iron overload; ii increasing with ineffective erythropoieis; iii and decreasing when level of transferrin iron utilisation is high. In TDT all three mechanisms increase NTBI levels because transferrin iron utilisation is suppressed by hypertransfusion. It is hypothesized that the transfusion regimen and target mean Hb may have a key impact on NTBI levels because high transfusion regimes may suppress the ‘sink’ effect of the erythron though decreased clearance of transferrin iron. In sickle cell disease (SCD without blood transfusion the anaemia results mainly from haemolysis rather than from ineffective erythropoiesis.2 Thus there is a tendency to iron depletion because of urinary iron loss from

  5. Iron, phytoplankton growth, and the carbon cycle.

    Science.gov (United States)

    Street, Joseph H; Paytan, Adina

    2005-01-01

    Iron is an essential nutrient for all living organisms. Iron is required for the synthesis of chlorophyll and of several photosynthetic electron transport proteins and for the reduction of CO2, SO4(2-), and NO3(-) during the photosynthetic production of organic compounds. Iron concentrations in vast areas of the ocean are very low (iron in oxic seawater. Low iron concentrations have been shown to limit primary production rates, biomass accumulation, and ecosystem structure in a variety of open-ocean environments, including the equatorial Pacific, the subarctic Pacific and the Southern Ocean and even in some coastal areas. Oceanic primary production, the transfer of carbon dioxide into organic carbon by photosynthetic plankton (phytoplankton), is one process by which atmospheric CO2 can be transferred to the deep ocean and sequestered for long periods of time. Accordingly, iron limitation of primary producers likely plays a major role in the global carbon cycle. It has been suggested that variations in oceanic primary productivity, spurred by changes in the deposition of iron in atmospheric dust, control atmospheric CO2 concentrations, and hence global climate, over glacial-interglacial timescales. A contemporary application of this "iron hypothesis" promotes the large-scale iron fertilization of ocean regions as a means of enhancing the ability of the ocean to store anthropogenic CO2 and mitigate 21st century climate change. Recent in situ iron enrichment experiments in the HNLC regions, however, cast doubt on the efficacy and advisability of iron fertilization schemes. The experiments have confirmed the role of iron in regulating primary productivity, but resulted in only small carbon export fluxes to the depths necessary for long-term sequestration. Above all, these experiments and other studies of iron biogeochemistry over the last two decades have begun to illustrate the great complexity of the ocean system. Attempts to engineer this system are likely to

  6. IRON METABOLISM IN THALASSEMIA AND SICKLE CELL DISEASE

    Directory of Open Access Journals (Sweden)

    Raffaella Mariani

    2009-10-01

    Full Text Available There are two main mechanisms by which iron overload develops in thalassemias: increased iron absorption due to ineffective erythropoiesis and blood transfusions. In nontransfused patients with severe thalassemia, abnormal dietary iron absorption increases body iron burden between 2 and 5 g per year. If regular transfusions are required, this doubles the rate of iron accumulation leading to earlier massive iron overload and iron-related damage. Iron metabolism largely differs between thalassemias and sickle cell disease, but chronic transfusion therapy partially normalize many of the disparities between the diseases, making iron overload an important issue to be considered in the management of patients with sickle cell disease too. The present review summarizes the actual knowledge on the regulatory pathways of iron homeostasis. In particular, the data presented indicate the inextricably link between erythropoiesis and iron metabolism and the key role of hepcidin in coordinating iron procurement according to erythropoietic requirement. The role of erythropoietin, hypoxia, erythroid-dependent soluble factors and iron in regulating hepcidin transcription are discussed as well as differences and similarities in iron homeostasis between thalassemia syndromes and sickle cell disease.

  7. Mitochondrial accumulation of APP and Abeta

    DEFF Research Database (Denmark)

    Pavlov, Pavel F; Petersen, Anna Camilla Hansson; Glaser, Elzbieta

    2009-01-01

    Accumulating evidence suggest that alterations in energy metabolism are among the earliest events that occur in the Alzheimer disease (AD) affected brain. Energy consumption is drastically decreased in the AD-affected regions of cerebral cortex and hippocampus pointing towards compromised mitocho...

  8. Brain derived neurotrophic factor

    DEFF Research Database (Denmark)

    Mitchelmore, Cathy; Gede, Lene

    2014-01-01

    Brain Derived Neurotrophic Factor (BDNF) is a neurotrophin with important functions in neuronal development and neuroplasticity. Accumulating evidence suggests that alterations in BDNF expression levels underlie a variety of psychiatric and neurological disorders. Indeed, BDNF therapies are curre......Brain Derived Neurotrophic Factor (BDNF) is a neurotrophin with important functions in neuronal development and neuroplasticity. Accumulating evidence suggests that alterations in BDNF expression levels underlie a variety of psychiatric and neurological disorders. Indeed, BDNF therapies...

  9. Tumoral distribution of long-circulating dextran-coated iron oxide nanoparticles in a rodent model.

    Science.gov (United States)

    Moore, A; Marecos, E; Bogdanov, A; Weissleder, R

    2000-02-01

    To investigate the accumulation and cellular uptake of long-circulating dextran-coated iron oxide (LCDIO) particles in malignant neoplasms in vivo. A gliosarcoma rodent model was established to determine the distribution of a model LCDIO preparation in tumors. LCDIO accumulation in tissue sections was evaluated with multichannel fluorescence microscopy with rhodaminated LCDIO, green fluorescent protein as a tumor marker, and Hoechst 33258 dye as an intravital endothelial stain. Uptake into tumor cells was corroborated with results of immunohistochemical and cell culture uptake experiments. The effect of intratumoral LCDIO uptake on magnetic resonance (MR) imaging signal intensity was evaluated with a 1.5-T superconducting magnet. Tumoral accumulation of LCDIO was 0.11% +/- 0.06 of the injected dose per gram of tissue in brain tumors and was sufficient for detection at MR imaging. In tumor sections, LCDIO was preferentially localized in tumor cells (49.0% +/- 4.6) but was also taken up by macrophages in tumors (21.0% +/- 3.1) and by endothelial cells in the areas of active angiogenesis (6.5% +/- 1.4). In cell culture, LCDIO uptake was strongly correlated with growth rate of tumor cell lines. Tumoral LCDIO accumulation was not negligible and helped explain MR imaging signal intensity changes observed in clinical trials. Microscopically, LCDIO accumulated predominantly in tumor cells and tumor-associated macrophages. Uptake into tumor cells appeared to be directly proportional to cellular proliferation rates.

  10. Iron and stony-iron meteorites

    DEFF Research Database (Denmark)

    Ruzicka, Alex M.; Haack, Henning; Chabot, Nancy L.

    2017-01-01

    By far most of the melted and differentiated planetesimals that have been sampled as meteorites are metal-rich iron meteorites or stony iron meteorites. The parent asteroids of these meteorites accreted early and differentiated shortly after the solar system formed, producing some of the oldest...... and interpretations for iron and stony iron meteorites (Plate 13.1). Such meteorites provide important constraints on the nature of metal-silicate separation and mixing in planetesimals undergoing partial to complete differentiation. They include iron meteorites that formed by the solidification of cores...... (fractionally crystallized irons), irons in which partly molten metal and silicates of diverse types were mixed together (silicate-bearing irons), stony irons in which partly molten metal and olivine from cores and mantles were mixed together (pallasites), and stony irons in which partly molten metal...

  11. The release of iron by Sertoli cells in culture

    NARCIS (Netherlands)

    Wauben-Penris, P. J.; Veldscholte, J.; van der Ende, A.; van der Donk, H. A.

    1988-01-01

    In seminiferous tubules, iron transport from the blood to the abluminal germinal cells must occur through the Sertoli cell cytoplasm. We investigated the release of previously accumulated iron by cultured Sertoli cells. We found that Sertoli cells contain easily releasable and less easily releasable

  12. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... Research Home / < Back To Health Topics / Iron-Deficiency Anemia Iron-Deficiency Anemia Leer en español What Is Iron-deficiency anemia ... cases, surgery may be advised. Treatments for Severe Iron-Deficiency Anemia Blood Transfusion If your iron-deficiency anemia is ...

  13. Iron-56 irradiation diminishes muscarinic but not {alpha}{sub 1}-adrenergic-stimulated low-K{sub m} GTPase in rat brain

    Energy Technology Data Exchange (ETDEWEB)

    Villalobos-Molina, R.; Joseph, J.A.; Rabin, B.M. [National Institute on Aging, Baltimore, MD (United States); Kandasamy, S.B.; Dalton, T.K.; Roth, G.S. [Armed Forces Radiobiology Research Institute, Bethesda, MD (United States)

    1994-12-01

    Initial findings from our laboratory have indicated that muscarinic enhancement of K{sup +}-evoked release of dopamine from perifused striatal slices is reduced after exposure to {sup 56}Fe-particle irradiation. This finding suggested that there is a radiation-induced deficit in muscarinic receptor sensitivity. Subsequent findings have indicated that at least part of the loss in sensitivity may occur as a result of alterations in the initial steps of the signal transduction process and involve muscarinic receptor-G protein coupling/uncoupling. The present study was carried out to localize this deficit further by determining carbachol-stimulated low-K{sub m} guanosine triphosphatase (GTPase) activity in striatal and hippocampal tissue obtained from rats exposed to 0, 0.1 or 1.0 Gy of {sup 56}Fe-particle irradiation. In addition, to examine the specificity of the effect of {sup 56}Fe-particle irradiation, {alpha}{sub 1}-adrenergic-stimulated low-K{sub m} GTPase activity was also examined in these tissues. The results showed that there was a high degree of specificity in the effects of {sup 56}Fe particles. Decrements were observed in muscarinic-stimulated low-K{sub m} GTPase in striatum but not in hippocampus, and {sup 56}Fe-particle irradiation did not affect {alpha}{sub 1}-adrenergic low-K{sub m} GTPase activity in either brain tissue. 24 refs., 2 figs.

  14. Effect of dietary iron on fetal growth in pregnant mice.

    Science.gov (United States)

    Hubbard, Andrea C; Bandyopadhyay, Sheila; Wojczyk, Boguslaw S; Spitalnik, Steven L; Hod, Eldad A; Prestia, Kevin A

    2013-04-01

    Iron deficiency is the most common nutritional disorder. Children and pregnant women are at highest risk for developing iron deficiency because of their increased iron requirements. Iron-deficiency anemia during pregnancy is associated with adverse effects on fetal development, including low birth weight, growth retardation, hypertension, intrauterine fetal death, neurologic impairment, and premature birth. We hypothesized that pregnant mice fed an iron-deficient diet would have a similar outcome regarding fetal growth to that of humans. To this end, we randomly assigned female C57BL/6 mice to consume 1 of 4 diets (high-iron-low-bioavailability, high-iron-high-bioavailability, iron-replete, and iron-deficient) for 4 wk before breeding, followed by euthanasia on day 17 to 18 of gestation. Compared with all other groups, dams fed the high-iron-high-bioavailability diet had significantly higher liver iron. Hct and Hgb levels in dams fed the iron-deficient diet were decreased by at least 2.5 g/dL as compared with those of all other groups. In addition, the percentage of viable pups among dams fed the iron-deficient diet was lower than that of all other groups. Finally, compared with all other groups, fetuses from dams fed the iron-deficient diet had lower fetal brain iron levels, shorter crown-rump lengths, and lower weights. In summary, mice fed an iron-deficient diet had similar hematologic values and fetal outcomes as those of iron-deficient humans, making this a useful model for studying iron-deficiency anemia during pregnancy.

  15. Microbial diversity and iron oxidation at Okuoku-hachikurou Onsen, a Japanese hot spring analog of Precambrian iron formations.

    Science.gov (United States)

    Ward, L M; Idei, A; Terajima, S; Kakegawa, T; Fischer, W W; McGlynn, S E

    2017-11-01

    Banded iron formations (BIFs) are rock deposits common in the Archean and Paleoproterozoic (and regionally Neoproterozoic) sedimentary successions. Multiple hypotheses for their deposition exist, principally invoking the precipitation of iron via the metabolic activities of oxygenic, photoferrotrophic, and/or aerobic iron-oxidizing bacteria. Some isolated environments support chemistry and mineralogy analogous to processes involved in BIF deposition, and their study can aid in untangling the factors that lead to iron precipitation. One such process analog system occurs at Okuoku-hachikurou (OHK) Onsen in Akita Prefecture, Japan. OHK is an iron- and CO2 -rich, circumneutral hot spring that produces a range of precipitated mineral textures containing fine laminae of aragonite and iron oxides that resemble BIF fabrics. Here, we have performed 16S rRNA gene amplicon sequencing of microbial communities across the range of microenvironments in OHK to describe the microbial diversity present and to gain insight into the cycling of iron, oxygen, and carbon in this ecosystem. These analyses suggest that productivity at OHK is based on aerobic iron-oxidizing Gallionellaceae. In contrast to other BIF analog sites, Cyanobacteria, anoxygenic phototrophs, and iron-reducing micro-organisms are present at only low abundances. These observations support a hypothesis where low growth yields and the high stoichiometry of iron oxidized per carbon fixed by aerobic iron-oxidizing chemoautotrophs like Gallionellaceae result in accumulation of iron oxide phases without stoichiometric buildup of organic matter. This system supports little dissimilatory iron reduction, further setting OHK apart from other process analog sites where iron oxidation is primarily driven by phototrophic organisms. This positions OHK as a study area where the controls on primary productivity in iron-rich environments can be further elucidated. When compared with geological data, the metabolisms and mineralogy at

  16. Siderophore-mediated iron trafficking in humans is regulated by iron

    Science.gov (United States)

    Liu, Zhuoming; Lanford, Robert; Mueller, Sebastian; Gerhard, Glenn S.; Luscieti, Sara; Sanchez, Mayka; Devireddy, L.

    2013-01-01

    Siderophores are best known as small iron binding molecules that facilitate microbial iron transport. In our previous study we identified a siderophore-like molecule in mammalian cells and found that its biogenesis is evolutionarily conserved. A member of the short chain dehydrogenase family of reductases, 3-OH butyrate dehydrogenase (BDH2) catalyzes a rate-limiting step in the biogenesis of the mammalian siderophore. We have shown that depletion of the mammalian siderophore by inhibiting expression of bdh2 results in abnormal accumulation of cellular iron and mitochondrial iron deficiency. These observations suggest that the mammalian siderophore is a critical regulator of cellular iron homeostasis and facilitates mitochondrial iron import. By utilizing bioinformatics, we identified an iron-responsive element (IRE; a stem-loop structure that regulates genes expression post-transcriptionally upon binding to iron regulatory proteins or IRPs) in the 3′-untranslated region (3′-UTR) of the human BDH2 (hBDH2) gene. In cultured cells as well as in patient samples we now demonstrate that the IRE confers iron-dependent regulation on hBDH2 and binds IRPs in RNA electrophoretic mobility shift assays. In addition, we show that the hBDH2 IRE associates with IRPs in cells and that abrogation of IRPs by RNAi eliminates the iron-dependent regulation of hBDH2 mRNA. The key physiologic implication is that iron-mediated post-transcriptional regulation of hBDH2 controls mitochondrial iron homeostasis in human cells. These observations provide a new and an unanticipated mechanism by which iron regulates its intracellular trafficking. PMID:22527885

  17. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... To Health Topics / Iron-Deficiency Anemia Iron-Deficiency Anemia What Is Iron-deficiency anemia is a common, ... all types of anemia . Signs and Symptoms of Anemia The most common symptom of all types of ...

  18. Iron and Your Child

    Science.gov (United States)

    ... extra iron in their diets. People following a vegetarian diet might also need added iron. What's Iron ... as Whole Milk? About Anemia Minerals What's a Vegetarian? Word! Anemia Anemia Food Labels Vitamins and Minerals ...

  19. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... of red blood cells, hemoglobin, and iron. Dietary Changes and Supplements Iron You may need iron supplements ... are improving. At your checkups, your doctor may change your medicines or supplements. He or she also ...

  20. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... or an inability to absorb enough iron from food. Overview Iron-deficiency anemia is a common type ... of the condition. Treatments may include dietary changes, medicines, and surgery. Severe iron-deficiency anemia may require ...

  1. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... Your doctor may advise you to eat more foods that are rich in iron. The best source ... iron from meat better than iron from nonmeat foods. However, some nonmeat foods also can help you ...

  2. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... the body. Iron-deficiency anemia usually develops over time if your body doesn't have enough iron ... because your need for iron increases during these times of growth and development. Inability To Absorb Enough ...

  3. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... or iron supplements, when used properly, can help prevent iron-deficiency anemia in infants and young children. ... in the diet. Too much milk also may prevent children's bodies from absorbing iron from other foods. ...

  4. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... have iron-deficiency anemia, you'll have a high level of transferrin that has no iron. Other ... may include dietary changes and supplements, medicines, and surgery. Severe iron-deficiency anemia may require a blood ...

  5. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... also may help treat iron-deficiency anemia. Medical History Your doctor will ask about your signs and ... much of the transferrin in your blood isn't carrying iron. If you have iron-deficiency anemia, ...

  6. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... or an inability to absorb enough iron from food. Overview Iron-deficiency anemia is a common type ... or an inability to absorb enough iron from food. Blood Loss When you lose blood, you lose ...

  7. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... iron in your body (a condition called iron overload). Too much iron in your body can damage ... talk about their experiences with clinical research. More Information Related Health Topics Anemia Blood Tests Blood Transfusion ...

  8. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... iron-deficiency anemia may require treatment in a hospital, blood transfusions , iron injections, or intravenous iron therapy. ... beans. Other lifestyle changes, such as getting enough sleep and exercising, also have helped Susan feel better. ...

  9. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... is low in iron. For this and other reasons, cow's milk isn't recommended for babies in ... iron in your body is low. For this reason, other iron tests also are done. Serum ferritin. ...

  10. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... been used. Transferrin level, or total iron-binding capacity. Transferrin is a protein that carries iron in your blood. Total iron-binding capacity measures how much of the transferrin in your ...

  11. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... Accessible Search Form Search the NHLBI, use the drop down list to select: the entire site, the ... enough iron. Your child's doctor may recommend iron drops. However, giving a child too much iron can ...

  12. Experimental oral iron administration: Histological investigations and expressions of iron handling proteins in rat retina with aging.

    Science.gov (United States)

    Kumar, Pankaj; Nag, Tapas Chandra; Jha, Kumar Abhiram; Dey, Sanjay Kumar; Kathpalia, Poorti; Maurya, Meenakshi; Gupta, Chandan Lal; Bhatia, Jagriti; Roy, Tara Sankar; Wadhwa, Shashi

    2017-12-01

    Iron is implicated in age-related macular degeneration (AMD). The aim of this study was to see if long-term, experimental iron administration with aging modifies retinal and choroidal structures and expressions of iron handling proteins, to understand some aspects of iron homeostasis. Male Wistar rats were fed with ferrous sulphate heptahydrate (500mg/kg body weight/week, oral; elemental iron availability: 20%) from 2 months of age onward until they were 19.5 month-old. At 8, 14 and 20 months of age, they were sacrificed and serum and retinal iron levels were detected by HPLC. Oxidative stress was analyzed by TBARS method. The retinas were examined for cell death (TUNEL), histology (electron microscopy) and the expressions of transferrin, transferrin receptor-1 [TFR-1], H- and L-ferritin. In control animals, at any age, there was no difference in the serum and retinal iron levels, but the latter increased significantly in 14- and 20 month-old iron-fed rats, indicating that retinal iron accumulation proceeds with progression of aging (>14 months). The serum and retinal TBARS levels increased significantly with progression of aging in experimental but not in control rats. There was significant damage to choriocapillaris, accumulation of phagosomes in retinal pigment epithelium and increased incidence of TUNEL+ cells in outer nuclear layer and vacuolation in inner nuclear layer (INL) of 20 month-aged experimental rats, compared to those in age-matched controls. Vacuolations in INL could indicate a long-term effect of iron accumulation in the inner retina. These events paralleled the increased expression of ferritins and transferrin and a decrease in the expression of TFR-1 in iron-fed rats with aging, thereby maintaining iron homeostasis in the retina. As some of these changes mimic with those happening in eyes with AMD, this model can be utilized to understand iron-induced pathophysiological changes in AMD. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Iron Overload in Patients Undergoing Hematopoietic Stem Cell Transplantation

    Directory of Open Access Journals (Sweden)

    Vinod Pullarkat

    2010-01-01

    Full Text Available Recipients of hematopoietic stem cell transplantation (HSCT frequently have iron overload resulting from chronic transfusion therapy for anemia. In some cases, for example, in patients with myelodysplastic syndromes and thalassemia, this can be further exacerbated by increased absorption of iron from the gut as a result of ineffective erythropoiesis. Accumulating evidence has established the negative impact of elevated pretransplantation serum ferritin, a surrogate marker of iron overload, on overall survival and nonrelapse mortality after HSCT. Complications of HSCT associated with iron overload include increased bacterial and fungal infections as well as sinusoidal obstruction syndrome and possibly other regimen-related toxicities. Based on current evidence, particular attention should be paid to prevention and management of iron overload in allogeneic HSCT candidates, especially in patients with thalassemia and myelodysplastic syndromes. The pathophysiology of iron overload in the HSCT patient and optimum strategies to deal with iron overload during and after HSCT require further study.

  14. Salinomycin kills cancer stem cells by sequestering iron in lysosomes

    Science.gov (United States)

    Mai, Trang Thi; Hamaï, Ahmed; Hienzsch, Antje; Cañeque, Tatiana; Müller, Sebastian; Wicinski, Julien; Cabaud, Olivier; Leroy, Christine; David, Amandine; Acevedo, Verónica; Ryo, Akihide; Ginestier, Christophe; Birnbaum, Daniel; Charafe-Jauffret, Emmanuelle; Codogno, Patrice; Mehrpour, Maryam; Rodriguez, Raphaël

    2017-10-01

    Cancer stem cells (CSCs) represent a subset of cells within tumours that exhibit self-renewal properties and the capacity to seed tumours. CSCs are typically refractory to conventional treatments and have been associated to metastasis and relapse. Salinomycin operates as a selective agent against CSCs through mechanisms that remain elusive. Here, we provide evidence that a synthetic derivative of salinomycin, which we named ironomycin (AM5), exhibits a more potent and selective activity against breast CSCs in vitro and in vivo, by accumulating and sequestering iron in lysosomes. In response to the ensuing cytoplasmic depletion of iron, cells triggered the degradation of ferritin in lysosomes, leading to further iron loading in this organelle. Iron-mediated production of reactive oxygen species promoted lysosomal membrane permeabilization, activating a cell death pathway consistent with ferroptosis. These findings reveal the prevalence of iron homeostasis in breast CSCs, pointing towards iron and iron-mediated processes as potential targets against these cells.

  15. Genetics Home Reference: iron-refractory iron deficiency anemia

    Science.gov (United States)

    ... refractory iron deficiency anemia Iron-refractory iron deficiency anemia Printable PDF Open All Close All Enable Javascript ... expand/collapse boxes. Description Iron-refractory iron deficiency anemia is one of many types of anemia , which ...

  16. Mapping of cellular iron using hyperspectral fluorescence imaging in a cellular model of Parkinson's disease

    Science.gov (United States)

    Oh, Eung Seok; Heo, Chaejeong; Kim, Ji Seon; Lee, Young Hee; Kim, Jong Min

    2013-05-01

    Parkinson's disease (PD) is characterized by progressive dopaminergic cell loss in the substantianigra (SN) and elevated iron levels demonstrated by autopsy and with 7-Tesla magnetic resonance imaging. Direct visualization of iron with live imaging techniques has not yet been successful. The aim of this study is to visualize and quantify the distribution of cellular iron using an intrinsic iron hyperspectral fluorescence signal. The 1-methyl-4-phenylpyridinium (MPP+)-induced cellular model of PD was established in SHSY5Y cells. The cells were exposed to iron by treatment with ferric ammonium citrate (FAC, 100 μM) for up to 6 hours. The hyperspectral fluorescence imaging signal of iron was examined usinga high- resolution dark-field optical microscope system with signal absorption for the visible/ near infrared (VNIR) spectral range. The 6-hour group showed heavy cellular iron deposition compared with the small amount of iron accumulation in the 1-hour group. The cellular iron was dispersed in a small, particulate form, whereas extracellular iron was detected in an aggregated form. In addition, iron particles were found to be concentrated on the cell membrane/edge of shrunken cells. The cellular iron accumulation readily occurred in MPP+-induced cells, which is consistent with previous studies demonstrating elevated iron levels in the SN in PD. This direct iron imaging methodology could be applied to analyze the physiological role of iron in PD, and its application might be expanded to various neurological disorders involving other metals, such as copper, manganese or zinc.

  17. Professional IronPython

    CERN Document Server

    Mueller, John Paul

    2010-01-01

    Part I: Introducing IronPython. This short part is designed to get the reader started using IronPython. It answers basic installation and usage questions, how to get help, and what makes IronPython different from other languages. The reader also discovers how to use familiar tools such as Visual Studio to work with IronPython and creates a very simple IronPython example. Most importantly, the reader becomes familiar with the IronPython environment and discovers how to use it.; Part II: Using the IronPython Language. In this part, the reader learns the IronPython language. It assumes that the r

  18. Iron and stony-iron meteorites

    DEFF Research Database (Denmark)

    Benedix, Gretchen K.; Haack, Henning; McCoy, T. J.

    2014-01-01

    Without iron and stony-iron meteorites, our chances of ever sampling the deep interior of a differentiated planetary object would be next to nil. Although we live on a planet with a very substantial core, we will never be able to sample it. Fortunately, asteroid collisions provide us with a rich...... sampling of the deep interiors of differentiated asteroids. Iron and stony-iron meteorites are fragments of a large number of asteroids that underwent significant geological processing in the early solar system. Parent bodies of iron and some stony-iron meteorites completed a geological evolution similar...... to that continuing on Earth – although on much smaller length- and timescales – with melting of the metal and silicates; differentiation into core, mantle, and crust; and probably extensive volcanism. Iron and stony-iron meteorites are our only available analogues to materials found in the deep interiors of Earth...

  19. Effect of montmorillonite on arsenic accumulation in common carp

    African Journals Online (AJOL)

    Yomi

    2012-02-01

    Feb 1, 2012 ... order: intestine>bone>gill>liver>muscle>brain (P<0.05), indicating accumulation of these tissues. When ..... interface. Colloids Surface A. 166: 153-159. Bains JS, Shaw CA (1997). Neurodegenerative disorders in humans: the role of glutathione in oxidative stress-mediated neuronal death. Brain Res. Rev.

  20. Oral Iron Prophylaxis in Pregnancy: Not Too Little and Not Too Much!

    Directory of Open Access Journals (Sweden)

    Nils Milman

    2012-01-01

    Full Text Available An adequate supply of iron is essential for normal development of the fetus and newborn child. Iron deficiency and iron deficiency anemia (IDA during pregnancy increase the risk of preterm birth and low birth weight. Iron is important for development of the fetal brain and cognitive abilities of the newborn. Children born to iron-deficient mothers will start their lives suffering from iron deficiency or even IDA. Oral iron prophylaxis to pregnant women improves iron status and prevents development of IDA. The Danish National Board of Health has since 1992 recommended prophylactic oral iron supplements to all pregnant women and the currently advocated dose is 40–50 mg ferrous iron taken between meals from 10 weeks gestation to delivery. However, 30–40 mg ferrous iron is probably an adequate dose in most affluent societies. In developed countries, individual iron prophylaxis guided by iron status (serum ferritin has physiological advantages compared to general iron prophylaxis. In contrast, in most developing countries, general iron prophylaxis is indicated, and higher doses of oral iron, for example, 60 mg ferrous iron or even more should be recommended, according to the present iron status situation in the specific populations of women of fertile age and pregnant women.

  1. [Asenic accumulation following realgar administration in rats].

    Science.gov (United States)

    Li, Chunying; Liang, Aihua; Wang, Jinhua; Xue, Baoyun; Li, Hua; Yang, Bin; Wang, Jingyu; Xie, Qing; Nilsen, Odd Georg; Zhang, Boli

    2011-07-01

    To explore arsenic accumulation and toxicity mechanism following long-term use of realgar and provide scientific basis for safety use of realgar in clinic. The realgar which was used in the study contains 90% insoluble asenic sulfide (As2S2) and 1.696 mg x kg(-1) soluble arsenic. Two separate experiments were performed: 1) Twenty-eight fasting SD rats were orally given a single dose of realgar at the dose of 0.8 g x kg(-1) and the other four rats were given ultra-filtrated water served as control group. Blood, hearts, livers, kidneys, lungs and brains of four rats were taken out at 0.5, 1, 2, 4, 8, 16, 36 h respectively after treatment. Asenic quantity of each organ or blood sample was measured. 2) Forty SD rats were randomly divided into four groups: control group and realgar 0.02, 0.08, 0.16 g x kg(-1) groups, each group containing 5 females and 5 males. The rats were intra-gastrically treated with realgar once a day for successively 90 days, while the control group was given ultra-filtrated water. Asenic amount in blood, liver, kidney and brain of each rat was measured in fasting rats at 16 h after last dosing. Asenic amount of blood, liver, kidney, heart, lung and brain increased after single dosing of realgar at dose of 0.16 g x kg(-1), with the order from high to low blood > kidney > lung > liver > heart > brain. Asenic amount was much higher in blood than that in other organs. The feature of asenic distribution in blood following realgar administration may be the basis for its use for leukemia Ninety-day oral treatment of realgar led to significant accumulation of asenic in blood, kidney, liver and brain. The highest asenic accumulation times was found in kidney followed by liver, which was assumed to be associated with nephrotoxicity and hepatotoxicity of realgar. The highest amount of asenic was observed in blood after 90 day's administration of realgar, and the amount of asenic in organs was in the order of blood > kidney > liver > brain. Asenic can be

  2. Iron from Zealandic bog iron ore -

    DEFF Research Database (Denmark)

    Lyngstrøm, Henriette Syrach

    2011-01-01

    og geologiske materiale, metallurgiske analyser og eksperimentel arkæologiske forsøg - konturerne af en jernproduktion med udgangspunkt i den sjællandske myremalm. The frequent application by archaeologists of Werner Christensen’s distribution map for the occurrence of bog iron ore in Denmark (1966...... are sketched of iron production based on bog iron ore from Zealand....

  3. APP expression, distribution and accumulation are altered by aluminum in a rodent model for Alzheimer's disease.

    Science.gov (United States)

    Walton, J R; Wang, M-X

    2009-11-01

    Up-regulated expression of amyloid precursor protein (APP) occurs early in the cascade of events that leads to amyloid plaque formation in the human brain. APP gene up-regulation, mediated by activated NF-kappaB, is a response to stress from nM concentrations of aluminum ions, aluminum-disregulated iron ions, reactive-oxygen species, cytokines, and physical trauma. We examined in vivo effects of aluminum on APP in aged rats, obtained from previously-reported longitudinal studies, that chronically ingested aluminum in amounts equivalent to total dietary aluminum levels that Americans routinely ingest. These rats exhibited two outcomes: one group remained cognitively-intact, scoring as well on a memory-discrimination task in old age as in middle age. The other developed cognitive deterioration, obtaining significantly lower mean performance scores in old age than in middle age and exhibiting abnormal behaviors associated with dementia. We compared the expression, distribution and accumulation of APP in hippocampal and cortical tissue of these two rat groups. Compared to results from cognitively-intact rats, hippocampal and cortical tissue from the cognitively-deteriorated rats showed elevated APP gene expression, significantly more dense APP deposits in cytoplasm of neural cells, and APP-immunoreactive neurites that were swollen and varicose. This study shows aluminum routinely derived from chronic oral ingestion, that gradually accumulates in brain regions important for memory-processing, is sufficient to increase APP levels in neural cells of those regions. Aluminum may thus launch the cascade that results in the formation of amyloid plaques in human brain.

  4. Recent advances in the understanding of iron overload in sideroblastic myelodysplastic syndrome.

    Science.gov (United States)

    Cuijpers, Maria L H; Raymakers, Reinier A P; Mackenzie, Marius A; de Witte, Theo J M; Swinkels, Dorine W

    2010-05-01

    Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal haematopoietic stem cell malignancies. A subgroup, the so-called sideroblastic MDS, shows ring sideroblasts in the bone marrow aspirate that represent mitochondrial iron accumulation. Patients with sideroblastic MDS also develop systemic iron overload and generally have a low-risk MDS. Therefore it is important to understand the mechanisms responsible for iron accumulation and the associated toxicity in these patients. Recently, low levels of the iron-regulatory peptide hepcidin were found to contribute to body iron overload in beta-thalassaemia patients. A similar mechanism may account for systemic iron accumulation in sideroblastic MDS. Mitochondrial iron accumulation is observed in several subtypes of MDS, and predominantly in refractory anaemia with ring sideroblasts. The presence of ring sideroblasts is also the diagnostic hallmark in patients with inherited forms of sideroblastic anaemia. The ever-increasing insights into the affected pathways in inherited sideroblastic anaemia may lead to a better comprehension of the pathogenesis of mitochondrial iron accumulation in MDS patients. Overall, an improved understanding of the mechanisms responsible for iron overload in MDS will lead to novel treatment strategies to reduce both systemic and mitochondrial iron overload, resulting in less tissue damage and more effective erythropoiesis.

  5. Serum iron test

    Science.gov (United States)

    Fe+2; Ferric ion; Fe++; Ferrous ion; Iron - serum; Anemia - serum iron; Hemochromatosis - serum iron ... A blood sample is needed. Iron levels are highest in the morning. Your health care provider will likely have you do this test in the morning.

  6. Iron deficiency anemia

    Science.gov (United States)

    Anemia - iron deficiency ... iron from old red blood cells. Iron deficiency anemia develops when your body's iron stores run low. ... You may have no symptoms if the anemia is mild. Most of the time, ... slowly. Symptoms may include: Feeling weak or tired more often ...

  7. Nutritional iron deficiency

    NARCIS (Netherlands)

    Zimmermann, M.B.; Hurrell, R.F.

    2007-01-01

    Iron deficiency is one of the leading risk factors for disability and death worldwide, affecting an estimated 2 billion people. Nutritional iron deficiency arises when physiological requirements cannot be met by iron absorption from diet. Dietary iron bioavailability is low in populations consuming

  8. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... as larger, full-term infants. Iron-fortified baby food or iron supplements, when used properly, can help prevent iron-deficiency ... Syndrome Other Resources Non-NHLBI Resources Anemia (MedlinePlus) "Dietary Supplement Fact Sheet: Iron" (Office of Dietary Supplements, National ...

  9. Moessbauer studies of frataxin role in iron-sulfur cluster assembly and dysfunction-related disease

    Energy Technology Data Exchange (ETDEWEB)

    Garcia-Serres, Ricardo [Universite Joseph Fourier (France); Clemancey, Martin [CNRS, UMR5249 (France); Oddou, Jean-Louis [Universite Joseph Fourier (France); Pastore, Annalisa [Medical Research Council National Institute for Medical Research (United Kingdom); Lesuisse, Emmanuel [Laboratoire Mitochondries, Metaux et Stress oxydant, Institut Jacques Monod, CNRS-Universite Paris (France); Latour, Jean-Marc, E-mail: jean-marc.latour@cea.fr [CEA, iRTSV, LCBM (France)

    2012-03-15

    Friedreich ataxia is a disease that is associated with defects in the gene coding for a small protein frataxin. Several different roles have been proposed for the protein, including iron chaperoning and iron storage. Moessbauer spectroscopy was used to probe these hypotheses. Iron accumulation in mutant mitochondria unable to assemble iron sulfur clusters proved to be insensitive to overexpression of frataxin, ruling out its potential involvement as an iron storage protein similar to ferritin. Rather, it was found that frataxin negatively regulates iron sulfur cluster assembly.

  10. Magnetic resonance imaging of reconstructed ferritin as an iron-induced pathological model system

    Energy Technology Data Exchange (ETDEWEB)

    Balejcikova, Lucia [Institute of Experimental Physics SAS, Watsonova 47, 040 01 Kosice (Slovakia); Institute of Measurement Science SAS, Dubravska cesta 9, 841 04 Bratislava 4 (Slovakia); Strbak, Oliver [Institute of Measurement Science SAS, Dubravska cesta 9, 841 04 Bratislava 4 (Slovakia); Biomedical Center Martin, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Mala Hora 4, 036 01 Martin (Slovakia); Baciak, Ladislav [Faculty of Chemical and Food Technology STU, Radlinskeho 9, 812 37 Bratislava (Slovakia); Kovac, Jozef [Institute of Experimental Physics SAS, Watsonova 47, 040 01 Kosice (Slovakia); Masarova, Marta; Krafcik, Andrej; Frollo, Ivan [Institute of Measurement Science SAS, Dubravska cesta 9, 841 04 Bratislava 4 (Slovakia); Dobrota, Dusan [Biomedical Center Martin, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Mala Hora 4, 036 01 Martin (Slovakia); Kopcansky, Peter [Institute of Experimental Physics SAS, Watsonova 47, 040 01 Kosice (Slovakia)

    2017-04-01

    Iron, an essential element of the human body, is a significant risk factor, particularly in the case of its concentration increasing above the specific limit. Therefore, iron is stored in the non-toxic form of the globular protein, ferritin, consisting of an apoferritin shell and iron core. Numerous studies confirmed the disruption of homeostasis and accumulation of iron in patients with various diseases (e.g. cancer, cardiovascular or neurological conditions), which is closely related to ferritin metabolism. Such iron imbalance enables the use of magnetic resonance imaging (MRI) as a sensitive technique for the detection of iron-based aggregates through changes in the relaxation times, followed by the change in the inherent image contrast. For our in vitrostudy, modified ferritins with different iron loadings were prepared by chemical reconstruction of the iron core in an apoferritin shell as pathological model systems. The magnetic properties of samples were studied using SQUID magnetometry, while the size distribution was detected via dynamic light scattering. We have shown that MRI could represent the most advantageous method for distinguishing native ferritin from reconstructed ferritin which, after future standardisation, could then be suitable for the diagnostics of diseases associated with iron accumulation. - Highlights: • MRI is the sensitive technique for detecting iron-based aggregates. • Reconstructed Ferritin is suitable model system of iron-related disorders. • MRI allow distinguish of native ferritin from reconstructed ferritin. • MRI could be useful for diagnostics of diseases associated with iron accumulation.

  11. Amyloid fibril systems reduce, stabilize and deliver bioavailable nanosized iron

    Science.gov (United States)

    Shen, Yi; Posavec, Lidija; Bolisetty, Sreenath; Hilty, Florentine M.; Nyström, Gustav; Kohlbrecher, Joachim; Hilbe, Monika; Rossi, Antonella; Baumgartner, Jeannine; Zimmermann, Michael B.; Mezzenga, Raffaele

    2017-07-01

    Iron-deficiency anaemia (IDA) is a major global public health problem. A sustainable and cost-effective strategy to reduce IDA is iron fortification of foods, but the most bioavailable fortificants cause adverse organoleptic changes in foods. Iron nanoparticles are a promising solution in food matrices, although their tendency to oxidize and rapidly aggregate in solution severely limits their use in fortification. Amyloid fibrils are protein aggregates initially known for their association with neurodegenerative disorders, but recently described in the context of biological functions in living organisms and emerging as unique biomaterial building blocks. Here, we show an original application for these protein fibrils as efficient carriers for iron fortification. We use biodegradable amyloid fibrils from β-lactoglobulin, an inexpensive milk protein with natural reducing effects, as anti-oxidizing nanocarriers and colloidal stabilizers for iron nanoparticles. The resulting hybrid material forms a stable protein-iron colloidal dispersion that undergoes rapid dissolution and releases iron ions during acidic and enzymatic in vitro digestion. Importantly, this hybrid shows high in vivo iron bioavailability, equivalent to ferrous sulfate in haemoglobin-repletion and stable-isotope studies in rats, but with reduced organoleptic changes in foods. Feeding the rats with these hybrid materials did not result in abnormal iron accumulation in any organs, or changes in whole blood glutathione concentrations, inferring their primary safety. Therefore, these iron-amyloid fibril hybrids emerge as novel, highly effective delivery systems for iron in both solid and liquid matrices.

  12. Brain Basics

    Medline Plus

    Full Text Available ... About Us Home > Health & Education > Educational Resources Brain Basics Introduction The Growing Brain The Working Brain Brain ... called the hypothalamic-pituitary-adrenal (HPA) axis. Brain Basics in Real Life Brain Basics in Real Life— ...

  13. Hydrogenation of iron in the early stage of Earth's evolution

    Science.gov (United States)

    Iizuka-Oku, Riko; Yagi, Takehiko; Gotou, Hirotada; Okuchi, Takuo; Hattori, Takanori; Sano-Furukawa, Asami

    2017-01-01

    Density of the Earth's core is lower than that of pure iron and the light element(s) in the core is a long-standing problem. Hydrogen is the most abundant element in the solar system and thus one of the important candidates. However, the dissolution process of hydrogen into iron remained unclear. Here we carry out high-pressure and high-temperature in situ neutron diffraction experiments and clarify that when the mixture of iron and hydrous minerals are heated, iron is hydrogenized soon after the hydrous mineral is dehydrated. This implies that early in the Earth's evolution, as the accumulated primordial material became hotter, the dissolution of hydrogen into iron occurred before any other materials melted. This suggests that hydrogen is likely the first light element dissolved into iron during the Earth's evolution and it may affect the behaviour of the other light elements in the later processes.

  14. Accumulation by Conservation

    NARCIS (Netherlands)

    Büscher, Bram; Fletcher, Robert

    2015-01-01

    Following the financial crisis and its aftermath, it is clear that the inherent contradictions of capitalist accumulation have become even more intense and plunged the global economy into unprecedented turmoil and urgency. Governments, business leaders and other elite agents are frantically

  15. Accumulation by Conservation

    NARCIS (Netherlands)

    Büscher, Bram; Fletcher, Robert

    2014-01-01

    Following the financial crisis and its aftermath, it is clear that the inherent contradictions of capitalist accumulation have become even more intense and plunged the global economy into unprecedented turmoil and urgency. Governments, business leaders and other elite agents are frantically

  16. Excessive sulfur supply reduces cadmium accumulation in brown rice (Oryza sativa L.)

    Energy Technology Data Exchange (ETDEWEB)

    Fan Jianling [State Key Laboratory of Soil and Sustainable Agriculture, Institute of Soil Science, Chinese Academy of Sciences, 71st East Beijing Road, Nanjing 210008 (China); College of Resources and Environment, Graduate University of Chinese Academy of Sciences, 19A, Yuquan Road, Beijing 100049 (China); Hu Zhengyi, E-mail: zhyhu@gucas.ac.c [College of Resources and Environment, Graduate University of Chinese Academy of Sciences, 19A, Yuquan Road, Beijing 100049 (China); Ziadi, Noura [Soils and Crops Research and Development Centre, Agriculture and Agri-Food Canada, 2560 Hochelaga Boulevard, Quebec, QC, G1V 2J3 (Canada); Xia Xu; Wu Congyanghui [State Key Laboratory of Soil and Sustainable Agriculture, Institute of Soil Science, Chinese Academy of Sciences, 71st East Beijing Road, Nanjing 210008 (China); College of Resources and Environment, Graduate University of Chinese Academy of Sciences, 19A, Yuquan Road, Beijing 100049 (China)

    2010-02-15

    Human activities have resulted in cadmium (Cd) and sulfur (S) accumulation in paddy soils in parts of southern China. A combined soil-sand pot experiment was conducted to investigate the influence of excessive S supply on iron plaque formation and Cd accumulation in rice plants, using two Cd levels (0, 1.5 mg kg{sup -1}) combined with three S concentrations (0, 60, 120 mg kg{sup -1}). The results showed that excessive S supply significantly decreased Cd accumulation in brown rice due to the decrease of Cd availability and the increase of glutathione in rice leaves. But excessive S supply obviously increased Cd accumulation in roots due to the decrease of iron plaque formation on the root surface of rice. Therefore, excessive S supply may result in loss of rice yield, but it could effectively reduce Cd accumulation in brown rice exposed to Cd contaminated soils. - Excessive sulfur reduces cadmium accumulation in brown rice.

  17. Mining iron: Iron uptake and transport in plants

    National Research Council Canada - National Science Library

    Kim, Sun A; Guerinot, Mary Lou

    2007-01-01

    .... Iron transport within plants is also tightly controlled. New information has emerged on transporters that play a role in xylem loading and phloem loading/unloading of iron, and on the iron chelators involved in iron homeostasis...

  18. Iron deficiency in Europe.

    Science.gov (United States)

    Hercberg, S; Preziosi, P; Galan, P

    2001-04-01

    In Europe, iron deficiency is considered to be one of the main nutritional deficiency disorders affecting large fractions of the population, particularly such physiological groups as children, menstruating women and pregnant women. Some factors such as type of contraception in women, blood donation or minor pathological blood loss (haemorrhoids, gynaecological bleeding...) considerably increase the difficulty of covering iron needs. Moreover, women, especially adolescents consuming low-energy diets, vegetarians and vegans are at high risk of iron deficiency. Although there is no evidence that an absence of iron stores has any adverse consequences, it does indicate that iron nutrition is borderline, since any further reduction in body iron is associated with a decrease in the level of functional compounds such as haemoglobin. The prevalence of iron-deficient anaemia has slightly decreased in infants and menstruating women. Some positive factors may have contributed to reducing the prevalence of iron-deficiency anaemia in some groups of population: the use of iron-fortified formulas and iron-fortified cereals; the use of oral contraceptives and increased enrichment of iron in several countries; and the use of iron supplements during pregnancy in some European countries. It is possible to prevent and control iron deficiency by counseling individuals and families about sound iron nutrition during infancy and beyond, and about iron supplementation during pregnancy, by screening persons on the basis of their risk for iron deficiency, and by treating and following up persons with presumptive iron deficiency. This may help to reduce manifestations of iron deficiency and thus improve public health. Evidence linking iron status with risk of cardiovascular disease or cancer is unconvincing and does not justify changes in food fortification or medical practice, particularly because the benefits of assuring adequate iron intake during growth and development are well established

  19. Mosses accumulate heavy metals from the substrata of coal ash

    Directory of Open Access Journals (Sweden)

    Vukojević Vanja

    2005-01-01

    Full Text Available Plants that are able to accumulate and tolerate extraordinarily high concentrations of heavy metals (hyperaccumulators can be used for phytoremediation (removal of contaminants from soils or phytomining (growing a crop of plants to harvest the metals. Two moss species, Bryum capillare Hedw. and Ceratodon purpureus Hedw., were tested as potential phytoremedies under in vivo conditions on a coal ash disposal site in the surroundings of Obrenovac (NW Serbia. The content of various heavy metals (iron, manganese zinc, lead, nickel, cadmium, and copper in the mosses and substrata were investigated over a period of three years. Iron and zinc were found to have the highest concentration in the mosses.

  20. Virtual iron concentration imaging based on dual-energy CT for noninvasive quantification and grading of liver iron content: An iron overload rabbit model study

    Energy Technology Data Exchange (ETDEWEB)

    Luo, Xian Fu; Yang, Yi; Xie, Xue Qian; Zhang, Huan; Chai, Wei Min; Yan, Fu Hua [Shanghai Jiao Tong University School of Medicine, Department of Radiology, Ruijin Hospital, Shanghai (China); Yan, Jing [Siemens Shanghai Medical Equipment Ltd., Shanghai (China); Wang, Li [Fudan University, Center of Analysis and Measurement, Shanghai (China); Schmidt, Bernhard [Siemens AG, Healthcare Sector, Forchheim (Germany)

    2015-09-15

    To assess the accuracy of liver iron content (LIC) quantification and grading ability associated with clinical LIC stratification using virtual iron concentration (VIC) imaging on dual-energy CT (DECT) in an iron overload rabbit model. Fifty-one rabbits were prepared as iron-loaded models by intravenous injection of iron dextran. DECT was performed at 80 and 140 kVp. VIC images were derived from an iron-specific algorithm. Postmortem LIC assessments were conducted on an inductively coupled plasma (ICP) spectrometer. Correlation between VIC and LIC was analyzed. VIC were stratified according to the corresponding clinical LIC thresholds of 1.8, 3.2, 7.0, and 15.0 mg Fe/g. Diagnostic performance of stratification was evaluated by receiver operating characteristic analysis. VIC linearly correlated with LIC (r = 0.977, P < 0.01). No significant difference was observed between VIC-derived LICs and ICP (P > 0.05). For the four clinical LIC thresholds, the corresponding cutoff values of VIC were 19.6, 25.3, 36.9, and 61.5 HU, respectively. The highest sensitivity (100 %) and specificity (100 %) were achieved at the threshold of 15.0 mg Fe/g. Virtual iron concentration imaging on DECT showed potential ability to accurately quantify and stratify hepatic iron accumulation in the iron overload rabbit model. (orig.)

  1. [Treatment of iron deficiency in predialysis state by low molecular weight iron dextran high doses intravenously].

    Science.gov (United States)

    Fievet, Patrick; Coppin, Mathilde; Brazier, François; Lefèvre, Magali; Stephan, Robin; Demontis, Renato

    2012-02-01

    Anemia is a common complication of chronic kidney disease (CKD) in predialysis stage. Iron deficiency is more common than in normal patients and plays a key role in the genesis of anemia. Its correction avoids the use of erythropoiesis stimulating agents (ESA) or reduces their dosage. Treatment with oral iron is often poorly tolerated and ineffective, necessitating the use of intravenous iron. New forms of injectable iron allow the use of high doses and correct iron deficiency in a single administration with consequent preservation of venous capital and lower costs. We studied the effectiveness of iron dextran of low molecular weight (LMWID) in high doses to correct iron deficiency and treat anemia in predialysis CKD patients. Twenty-nine doses of 500 to 1600 mg were administered to 25 patients followed for CKD (GFR between 60 and 10 ml/min per 1.73 m(2)), selected on biological criteria of iron deficiency defined by a ratio of transferrin saturation (TSAT) iron overload. Their serum ferritin was higher than the rest of the population before treatment, while the TSAT was no different, reflecting a functional deficiency. Their hemoglobin did not increase after treatment in contrast to the rest of the population suggesting the unavailability of iron for erythropoiesis with accumulation in the reticuloendothelial system. Renal function did not change significantly and there were no cases of acute renal failure. No immediate side effect was observed. Three patients presented delayed reactions to such self-limiting myalgia and arthralgia. No venous inflammatory reaction was noted. The administration of high doses of LMWID is effective in treating anemia of CKD in the predialysis stage with a satisfactory tolerance, without affecting kidney function and helps preserve the venous capital. It should be reserved for patients whose serum ferritin is less than or equal to 150 μg/L. Copyright © 2011 Association Société de néphrologie. Published by Elsevier SAS. All rights

  2. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... can lead to heart problems, infections, problems with growth and development in children, and other complications. Infants ... blood transfusions , iron injections, or intravenous iron therapy. Rate This Content: NEXT >> Featured Video Living With and ...

  3. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... less hemoglobin than normal. Iron-deficiency anemia can cause fatigue (tiredness), shortness of breath, chest pain, and ... iron-deficiency anemia. Treatment will depend on the cause and severity of the condition. Treatments may include ...

  4. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... also may help treat iron-deficiency anemia. Medical History Your doctor will ask about your signs and ... It must be done in a hospital or clinic by experienced staff. Iron therapy usually is given ...

  5. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... usually can successfully treat iron-deficiency anemia. Treatment will depend on the cause and severity of the ... about a healthy diet and food choices that will help your child get enough iron. Your child's ...

  6. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... you don't have enough iron in your body. Low iron levels usually are due to blood ... remove carbon dioxide (a waste product) from your body. Anemia also can occur if your red blood ...

  7. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... or soil, or drinking water that contains lead. Teens Teens are at risk for iron-deficiency anemia ... for increased blood volume and for the fetus' growth. About half of all pregnant women develop iron- ...

  8. Total iron binding capacity

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/article/003489.htm Total iron binding capacity To use the sharing features on this page, please enable JavaScript. Total iron binding capacity (TIBC) is a blood test to ...

  9. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... food. Overview Iron-deficiency anemia is a common type of anemia . The term "anemia" usually refers to ... also may lead to iron-deficiency anemia. This type of blood loss isn't always obvious, and ...

  10. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... condition. Treatments may include dietary changes, medicines, and surgery. Severe iron-deficiency anemia may require treatment in ... Urinary tract bleeding Blood loss from severe injuries, surgery, or frequent blood drawings also can cause iron- ...

  11. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... and Blood Safety Sleep Science and Sleep Disorders Lung Diseases Heart and Vascular Diseases Precision Medicine Activities ... iron-rich protein that carries oxygen from the lungs to the rest of the body. Iron-deficiency ...

  12. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... condition. Women Women of childbearing age are at higher risk for iron-deficiency anemia because of blood ... iron-deficiency anemia. Pregnant women also are at higher risk for the condition because they need twice ...

  13. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... help prevent overdosing in children. Because recent research supports concerns that iron deficiency during infancy and childhood ... treat iron-deficiency anemia. These doctors include pediatricians, family doctors, gynecologists/obstetricians, and internal medicine specialists. A ...

  14. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... more information about diet and supplements, go to "How Is Iron-Deficiency Anemia Treated?" Infants and young ... who should be screened for iron deficiency, and how often: Girls aged 12 to 18 and women ...

  15. Iron supplements (image)

    Science.gov (United States)

    The mineral iron is an essential nutrient for humans because it is part of blood cells, which carry oxygen to all body cells. There is no conclusive evidence that iron supplements contribute to heart attacks.

  16. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... low iron levels in women. Internal bleeding (bleeding inside the body) also may lead to iron-deficiency ... a diagnosis, look for a cause, and find out how severe the condition is. Complete Blood Count ...

  17. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... inability to absorb enough iron from food. Blood Loss When you lose blood, you lose iron. If ... produce hemoglobin. Tests and Procedures for Gastrointestinal Blood Loss To check whether internal bleeding is causing your ...

  18. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... the cause and severity of the condition. Treatments may include dietary changes, medicines, and surgery. Severe iron-deficiency anemia may require treatment in a hospital, blood transfusions , iron ...

  19. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... and other symptoms. Severe iron-deficiency anemia can lead to heart problems, infections, problems with growth and ... Internal bleeding (bleeding inside the body) also may lead to iron-deficiency anemia. This type of blood ...

  20. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... total amount of iron you need every day. Vitamin C Vitamin C helps the body absorb iron. Good sources of vitamin C are vegetables and fruits, especially citrus fruits. Citrus ...

  1. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... Deficiency Anemia Explore Iron-Deficiency Anemia What Is... CAUSES WHO IS AT RISK SIGNS & SYMPTOMS DIAGNOSIS TREATMENTS ... less hemoglobin than normal. Iron-deficiency anemia can cause fatigue (tiredness), shortness of breath, chest pain, and ...

  2. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... of fiber can slow the absorption of iron. Screening and Prevention Eating a well-balanced diet that ... pregnant women, medical care during pregnancy usually includes screening for anemia. Also, your doctor may prescribe iron ...

  3. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... iron-rich protein that carries oxygen from the lungs to the rest of the body. Iron-deficiency ... 2011 This video—presented by the National Heart, Lung, and Blood Institute, part of the National Institutes ...

  4. Iron in diet

    Science.gov (United States)

    ... iron; Ferric acid; Ferrous acid; Ferritin Images Iron supplements References Institute of Medicine, Food and Nutrition Board. Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, ...

  5. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... drawings also can cause iron-deficiency anemia. Poor Diet The best sources of iron are meat, poultry, ... also checks the number of red blood cells, white blood cells, and platelets in your blood. Abnormal ...

  6. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... coped with having iron-deficiency anemia. Prior to her diagnosis, Susan had symptoms such as tiredness, poor skin tone, dizziness, and depression. After her doctor diagnosed her with iron-deficiency anemia, Susan ...

  7. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... specialists also may help treat iron-deficiency anemia. Medical History Your doctor will ask about your signs ... information, go to the Health Topics Blood Transfusion article. Iron Therapy If you have severe anemia, your ...

  8. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... an inability to absorb enough iron from food. Blood Loss When you lose blood, you lose iron. ... find out how severe the condition is. Complete Blood Count Often, the first test used to diagnose ...

  9. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... drawings also can cause iron-deficiency anemia. Poor Diet The best sources of iron are meat, poultry, ... other dark green leafy vegetables Prune juice The Nutrition Facts labels on packaged foods will show how ...

  10. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... Poor Diet The best sources of iron are meat, poultry, fish, and iron-fortified foods (foods that ... happen if you: Follow a diet that excludes meat and fish, which are the best sources of ...

  11. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... muh-glow-bin). Hemoglobin is an iron-rich protein that carries oxygen from the lungs to the ... hemoglobin than normal. Hemoglobin is an iron-rich protein in red blood cells. It helps red blood ...

  12. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... screened for iron deficiency, and how often: Girls aged 12 to 18 and women of childbearing age ... For this treatment, iron is injected into a muscle or an IV line in one of your ...

  13. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... stomach also can interfere with iron absorption. Risk Factors Infants and Young Children Infants and young children ... blood loss during their monthly periods Other risk factors for iron-deficiency anemia The Centers for Disease ...

  14. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... done in a hospital or clinic by experienced staff. Iron therapy usually is given to people who ... Resources Anemia (MedlinePlus) "Dietary Supplement Fact Sheet: Iron" (Office of Dietary Supplements, National Institutes of Health) Building ...

  15. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... For this treatment, iron is injected into a muscle or an IV line in one of your ... body can damage your organs. You may have fatigue (tiredness) and other symptoms of iron-deficiency anemia ...

  16. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... during these times of growth and development. Inability To Absorb Enough Iron Even if you have enough ... green vegetables like turnip greens and spinach. Treatment To Stop Bleeding If blood loss is causing iron- ...

  17. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... intravenous iron therapy. Rate This Content: NEXT >> Featured Video Living With and Managing Iron-Deficiency Anemia 05/18/2011 This video—presented by the National Heart, Lung, and Blood ...

  18. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... absorption of iron. Screening and Prevention Eating a well-balanced diet that includes iron-rich foods may ... the strength of a few medicines and how well they work. Other fruits rich in vitamin C ...

  19. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... prevent children's bodies from absorbing iron from other foods. Children who have lead in their blood also may be at risk for iron-deficiency anemia. Lead can interfere with ...

  20. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... easily treated condition that occurs if you don't have enough iron in your body. Low iron ... can occur if your red blood cells don't contain enough hemoglobin (HEE-muh-glow-bin). Hemoglobin ...

  1. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... Studies NHLBI Trials Clinical Trial Websites News & Resources Press Releases Spotlight On Research NHLBI In the News ... you don't have enough iron in your body. Low iron levels usually are due to blood ...

  2. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... Diseases Heart and Vascular Diseases Precision Medicine Activities Obesity, Nutrition, and Physical Activity Population and Epidemiology Studies ... or an inability to absorb enough iron from food. Overview Iron-deficiency anemia is a common type ...

  3. Antiproton Accumulator (AA)

    CERN Multimedia

    Photographic Service

    1980-01-01

    The AA in its final stage of construction, before it disappeared from view under concrete shielding. Antiprotons were first injected, stochastically cooled and accumulated in July 1980. From 1981 on, the AA provided antiprotons for collisions with protons, first in the ISR, then in the SPS Collider. From 1983 on, it also sent antiprotons, via the PS, to the Low-Energy Antiproton Ring (LEAR). The AA was dismantled in 1997 and shipped to Japan.

  4. Graphitized Cast Irons

    Science.gov (United States)

    Silman, G. I.; Makarenko, K. V.

    2014-05-01

    An analytical review of data on general-purpose grayed cast iron with different forms of graphite (lamellar, vermicular, globular, flaked) is presented. Grades of cast iron, their compositions, special features of structure of the graphite, and properties of gray, high-strength and malleable irons are described. The data on the kinds of iron considered are compared with those stipulated in international and some national standards.

  5. The Organization of Controller Motifs Leading to Robust Plant Iron Homeostasis.

    Directory of Open Access Journals (Sweden)

    Oleg Agafonov

    Full Text Available Iron is an essential element needed by all organisms for growth and development. Because iron becomes toxic at higher concentrations iron is under homeostatic control. Plants face also the problem that iron in the soil is tightly bound to oxygen and difficult to access. Plants have therefore developed special mechanisms for iron uptake and regulation. During the last years key components of plant iron regulation have been identified. How these components integrate and maintain robust iron homeostasis is presently not well understood. Here we use a computational approach to identify mechanisms for robust iron homeostasis in non-graminaceous plants. In comparison with experimental results certain control arrangements can be eliminated, among them that iron homeostasis is solely based on an iron-dependent degradation of the transporter IRT1. Recent IRT1 overexpression experiments suggested that IRT1-degradation is iron-independent. This suggestion appears to be misleading. We show that iron signaling pathways under IRT1 overexpression conditions become saturated, leading to a breakdown in iron regulation and to the observed iron-independent degradation of IRT1. A model, which complies with experimental data places the regulation of cytosolic iron at the transcript level of the transcription factor FIT. Including the experimental observation that FIT induces inhibition of IRT1 turnover we found a significant improvement in the system's response time, suggesting a functional role for the FIT-mediated inhibition of IRT1 degradation. By combining iron uptake with storage and remobilization mechanisms a model is obtained which in a concerted manner integrates iron uptake, storage and remobilization. In agreement with experiments the model does not store iron during its high-affinity uptake. As an iron biofortification approach we discuss the possibility how iron can be accumulated even during high-affinity uptake.

  6. Effects of intracerebroventricular injection of iron dextran on the iron concentration and divalent metal transporter 1 expression in the caudate putamen and substantia nigra of rats.

    Science.gov (United States)

    Yu, Peng; Chang, Yan-Zhong; Miao, Wei; Wang, Shu-Min; Cui, Rui; Qian, Zhong-Ming; Ke, Ya; Duan, Xiang-Lin

    2009-02-01

    The cellular localization of DMT1 and its functional characterization suggest that DMT1 may play an important role in the physiological brain iron transport. But the regulation of DMT1 expression by iron in the brain is still not clearly understood. In this study, both the contents of ferric and ferrous iron as well as DMT1 expression were evaluated in CPu and SN after ICV of 500 microg iron dextran/rat/day for 3 or 7 days. It was found that the iron levels in CPu and SN were not altered obviously until ICV for 7 days. Immunohistochemistry results indicated that the expression of DMT1 (-IRE) in CPu and SN was not altered significantly after 3 days of ICV. Whereas the expression of DMT1 (-IRE) decreased significantly after 7 days of ICV when ferrous iron was increased significantly. Contrary to that of DMT1 (-IRE) in the same regions, there were no significant alterations in DMT1 (+IRE) expression in CPu and SN in spite of the existence of the altered iron levels, compared with that of control groups. The results demonstrate that DMT1 (-IRE) expression was correlated probably with brain iron levels; especially, its regulation was correlated with ferrous iron (not ferric iron) in CPu and SN in adult rats, compared with those of saline-injected control rats. The effect of ferrous iron on the expression of DMT1 (-IRE) in the brain also suggests that it might play a major physiological role in brain iron uptake and transport, but further studies are needed to clarify these issues. (c) 2008 Wiley-Liss, Inc.

  7. Selenium accumulation by plants.

    Science.gov (United States)

    White, Philip J

    2016-02-01

    Selenium (Se) is an essential mineral element for animals and humans, which they acquire largely from plants. The Se concentration in edible plants is determined by the Se phytoavailability in soils. Selenium is not an essential element for plants, but excessive Se can be toxic. Thus, soil Se phytoavailability determines the ecology of plants. Most plants cannot grow on seleniferous soils. Most plants that grow on seleniferous soils accumulate plant species have evolved tolerance to Se, and commonly accumulate tissue Se concentrations >100 mg Se kg(-1) dry matter. These plants are considered to be Se accumulators. Some species can even accumulate Se concentrations of 1000-15 000 mg Se kg(-1 )dry matter and are called Se hyperaccumulators. This article provides an overview of Se uptake, translocation and metabolism in plants and highlights the possible genetic basis of differences in these between and within plant species. The review focuses initially on adaptations allowing plants to tolerate large Se concentrations in their tissues and the evolutionary origin of species that hyperaccumulate Se. It then describes the variation in tissue Se concentrations between and within angiosperm species and identifies genes encoding enzymes limiting the rates of incorporation of Se into organic compounds and chromosomal loci that might enable the development of crops with greater Se concentrations in their edible portions. Finally, it discusses transgenic approaches enabling plants to tolerate greater Se concentrations in the rhizosphere and in their tissues. The trait of Se hyperaccumulation has evolved several times in separate angiosperm clades. The ability to tolerate large tissue Se concentrations is primarily related to the ability to divert Se away from the accumulation of selenocysteine and selenomethionine, which might be incorporated into non-functional proteins, through the synthesis of less toxic Se metabilites. There is potential to breed or select crops

  8. Brain Basics

    Medline Plus

    Full Text Available ... Brain Research Glossary Brain Basics (PDF, 10 pages) Introduction Watch the Brain Basics video Welcome. Brain Basics provides information on how the brain works, how mental illnesses ...

  9. Brain Basics

    Science.gov (United States)

    ... Events About Us Home > Health & Education > Educational Resources Brain Basics Introduction The Growing Brain The Working Brain ... to mental disorders, such as depression. The Growing Brain Inside the Brain: Neurons & Neural Circuits Neurons are ...

  10. Brain Basics

    Medline Plus

    Full Text Available ... Events About Us Home > Health & Education > Educational Resources Brain Basics Introduction The Growing Brain The Working Brain ... to mental disorders, such as depression. The Growing Brain Inside the Brain: Neurons & Neural Circuits Neurons are ...

  11. Brain Basics

    Medline Plus

    Full Text Available ... Brain Basics provides information on how the brain works, how mental illnesses are disorders of the brain, ... learning more about how the brain grows and works in healthy people, and how normal brain development ...

  12. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... the best sources of iron. Follow a high-fiber diet. Large amounts of fiber can slow the absorption of iron. Screening and Prevention Eating a well-balanced diet that includes iron-rich foods may help you ...

  13. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... diet. Young children who drink a lot of cow's milk may be at risk for iron-deficiency anemia. ... her risk for iron-deficiency anemia. For example, cow's milk is low in iron. For this and other ...

  14. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... Organization NHLBI Director Budget, Planning, & Legislative Advisory Committees Jobs Contact Us FAQs Home » Iron-Deficiency Anemia Explore ... the body. Iron-deficiency anemia usually develops over time if your body doesn't have enough iron ...

  15. Iron and Immunity

    NARCIS (Netherlands)

    Verbon, E.H.; Trapet, P.L.; Stringlis, I.|info:eu-repo/dai/nl/41185206X; Kruijs, Sophie; Bakker, P.A.H.M.|info:eu-repo/dai/nl/074744623; Pieterse, C.M.J.|info:eu-repo/dai/nl/113115113

    2017-01-01

    Iron is an essential nutrient for most life on Earth because it functions as a crucial redox catalyst in many cellular processes. However, when present in excess iron can lead to the formation of harmful hydroxyl radicals. Hence, the cellular iron balance must be tightly controlled. Perturbation of

  16. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... To Health Topics / Iron-Deficiency Anemia Iron-Deficiency Anemia Leer en español What Is Iron-deficiency anemia ... all types of anemia . Signs and Symptoms of Anemia The most common symptom of all types of ...

  17. Iron Stain on Wood

    Science.gov (United States)

    Mark Knaebe

    2013-01-01

    Iron stain, an unsightly blue–black or gray discoloration, can occur on nearly all woods. Oak, redwood, cypress, and cedar are particularly prone to iron stain because these woods contain large amounts of tannin-like extractives. The discoloration is caused by a chemical reaction between extractives in the wood and iron in steel products, such as nails, screws, and...

  18. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... page from the NHLBI on Twitter. What Is Iron-Deficiency Anemia? Español Iron-deficiency anemia is a ... Content: NEXT >> Featured Video Living With and Managing Iron-Deficiency Anemia 05/18/2011 This video—presented ...

  19. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... iron-rich foods in the diet. Too much milk also may prevent children's bodies from absorbing iron from other foods. Children who have lead in their blood also may be at risk for iron-deficiency anemia. Lead can interfere with the body's ability to make hemoglobin. Lead may get into the body from ...

  20. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... Tumblr. Share this page from the NHLBI on Twitter. What Is Iron-Deficiency Anemia? Español Iron-deficiency ... Iron-Deficiency Anemia article. Updated: March 26, 2014 Twitter Facebook YouTube Google+ SITE INDEX ACCESSIBILITY PRIVACY STATEMENT ...

  1. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... Site Health Topics News & Resources Intramural Research ... Is Iron-deficiency anemia is a common, easily treated condition that occurs if you don't have enough iron in your body. Low iron levels usually are due to blood loss, ...

  2. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... other dark green leafy vegetables Prune juice The Nutrition Facts labels on packaged foods will show how much iron the items contain. The amount is given as a percentage of the total amount of iron you need every day. Vitamin C Vitamin C helps the body absorb iron. ...

  3. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... the NHLBI on Twitter. What Is Iron-Deficiency Anemia? Español Iron-deficiency anemia is a common, easily ... Featured Video Living With and Managing Iron-Deficiency Anemia 05/18/2011 This video—presented by the ...

  4. Iron homeostasis during pregnancy.

    Science.gov (United States)

    Fisher, Allison L; Nemeth, Elizabeta

    2017-12-01

    During pregnancy, iron needs to increase substantially to support fetoplacental development and maternal adaptation to pregnancy. To meet these iron requirements, both dietary iron absorption and the mobilization of iron from stores increase, a mechanism that is in large part dependent on the iron-regulatory hormone hepcidin. In healthy human pregnancies, maternal hepcidin concentrations are suppressed in the second and third trimesters, thereby facilitating an increased supply of iron into the circulation. The mechanism of maternal hepcidin suppression in pregnancy is unknown, but hepcidin regulation by the known stimuli (i.e., iron, erythropoietic activity, and inflammation) appears to be preserved during pregnancy. Inappropriately increased maternal hepcidin during pregnancy can compromise the iron availability for placental transfer and impair the efficacy of iron supplementation. The role of fetal hepcidin in the regulation of placental iron transfer still remains to be characterized. This review summarizes the current understanding and addresses the gaps in knowledge about gestational changes in hematologic and iron variables and regulatory aspects of maternal, fetal, and placental iron homeostasis. © 2017 American Society for Nutrition.

  5. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... have severe anemia, your doctor may recommend iron therapy. For this treatment, iron is injected into a muscle or an IV line in one of your blood vessels. IV iron therapy presents some safety concerns. It must be done ...

  6. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... blood transfusions , iron injections, or intravenous iron therapy. Rate This Content: NEXT >> Featured Video Living With and Managing Iron-Deficiency Anemia 05/18/2011 This video—presented by the National Heart, Lung, and Blood Institute, part of the National ...

  7. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... the body. Iron-deficiency anemia usually develops over time if your body doesn't have enough iron ... Institutes of Health—shows how Susan, a full-time worker and student, has coped with having iron- ...

  8. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... iron-deficiency anemia, especially if they have: A history of iron-deficiency anemia Heavy blood loss during their monthly periods Other risk factors for iron-deficiency anemia The Centers for Disease Control and Prevention (CDC) has developed guidelines for who ...

  9. Microbial Biosignatures in High Iron Thermal Springs

    Science.gov (United States)

    Parenteau, M. N.; Embaye, T.; Jahnke, L. L.; Cady, S. L.

    2003-12-01

    The emerging anoxic source waters at Chocolate Pots hot springs in Yellowstone National Park contain 2.6 to 11.2 mg/L Fe(II) and are 51-54° C and pH 5.5-6.0. These waters flow down the accumulating iron deposits and over three major phototrophic mat communities: Synechococcus/Chloroflexus at 51-54° C, Pseudanabaena at 51-54° C, and a narrow Oscillatoria at 36-45° C. We are assessing the contribution of the phototrophs to biosignature formation in this high iron system. These biosignatures can be used to assess the biological contribution to ancient iron deposits on Earth (e.g. Precambrian Banded Iron Formations) and, potentially, to those found on Mars. Most studies to date have focused on chemotrophic iron-oxidizing communities; however, recent research has demonstrated that phototrophs have a significant physiological impact on these iron thermal springs (Pierson et al. 1999, Pierson and Parenteau 2000, and Trouwborst et al., 2003). We completed a survey of the microfossils, biominerals, biofabrics, and lipid biomarkers in the phototrophic mats and stromatolitic iron deposits using scanning and transmission electron microscopy (SEM and TEM), energy dispersive spectrometry (EDS), powder X-ray diffraction (XRD), and gas chromatography-mass spectroscopy (GC-MS). The Synechococcus/Chloroflexus mat was heavily encrusted with iron silicates while the narrow Oscillatoria mat was encrusted primarily with iron oxides. Encrustation of the cells increased with depth in the mats. Amorphous 2-line ferrihydrite is the primary precipitate in the spring and the only iron oxide mineral associated with the mats. Goethite, hematite, and siderite were detected in dry sediment samples on the face of the main iron deposit. Analysis of polar lipid fatty acid methyl esters (FAME) generated a suite of lipid biomarkers. The Synechococcus/Chloroflexus mat contained two mono-unsaturated isomers of n-C18:1 with smaller amounts of polyunsaturated n-C18:2, characteristic of cyanobacteria

  10. Plasma protein haptoglobin modulates renal iron loading

    DEFF Research Database (Denmark)

    Fagoonee, Sharmila; Gburek, Jakub; Hirsch, Emilio

    2005-01-01

    Haptoglobin is the plasma protein with the highest binding affinity for hemoglobin. The strength of hemoglobin binding and the existence of a specific receptor for the haptoglobin-hemoglobin complex in the monocyte/macrophage system clearly suggest that haptoglobin may have a crucial role in heme...... morphological and functional parameters of renal damage. These data demonstrate that haptoglobin crucially prevents glomerular filtration of hemoglobin and, consequently, renal iron loading during aging and following acute plasma heme-protein overload....... distribution of hemoglobin in haptoglobin-deficient mice resulted in abnormal iron deposits in proximal tubules during aging. Moreover, iron also accumulated in proximal tubules after renal ischemia-reperfusion injury or after an acute plasma heme-protein overload caused by muscle injury, without affecting...

  11. Cardiac protection by preconditioning is generated via an iron-signal created by proteasomal degradation of iron proteins.

    Directory of Open Access Journals (Sweden)

    Baruch E Bulvik

    Full Text Available Ischemia associated injury of the myocardium is caused by oxidative damage during reperfusion. Myocardial protection by ischemic preconditioning (IPC was shown to be mediated by a transient 'iron-signal' that leads to the accumulation of apoferritin and sequestration of reactive iron released during the ischemia. Here we identified the source of this 'iron signal' and evaluated its role in the mechanisms of cardiac protection by hypoxic preconditioning. Rat hearts were retrogradely perfused and the effect of proteasomal and lysosomal protease inhibitors on ferritin levels were measured. The iron-signal was abolished, ferritin levels were not increased and cardiac protection was diminished by inhibition of the proteasome prior to IPC. Similarly, double amounts of ferritin and better recovery after ex vivo ischemia-and-reperfusion (I/R were found in hearts from in vivo hypoxia pre-conditioned animals. IPC followed by normoxic perfusion for 30 min ('delay' prior to I/R caused a reduced ferritin accumulation at the end of the ischemia phase and reduced protection. Full restoration of the IPC-mediated cardiac protection was achieved by employing lysosomal inhibitors during the 'delay'. In conclusion, proteasomal protein degradation of iron-proteins causes the generation of the 'iron-signal' by IPC, ensuing de-novo apoferritin synthesis and thus, sequestering reactive iron. Lysosomal proteases are involved in subsequent ferritin breakdown as revealed by the use of specific pathway inhibitors during the 'delay'. We suggest that proteasomal iron-protein degradation is a stress response causing an expeditious cytosolic iron release thus, altering iron homeostasis to protect the myocardium during I/R, while lysosomal ferritin degradation is part of housekeeping iron homeostasis.

  12. Update on the use of deferasirox in the management of iron overload

    Directory of Open Access Journals (Sweden)

    Ali Taher

    2009-10-01

    Full Text Available Ali Taher,1 Maria Domenica Cappellini21American University of Beirut, Beirut, Lebanon; 2Universitá di Milano, Policlinico Foundation IRCCS, Milan, ItalyAbstract: Regular blood transfusions as supportive care for patients with chronic anemia inevitably lead to iron overload as humans cannot actively remove excess iron. The cumulative effects of iron overload cause significant morbidity and mortality if not effectively treated with chelation therapy. Based on a comprehensive clinical development program, the once-daily, oral iron chelator deferasirox (Exjade® is approved for the treatment of transfusional iron overload in adult and pediatric patients with various transfusion-dependent anemias, including β-thalassemia and the myelodysplastic syndromes. Deferasirox dose should be titrated for each individual patient based on transfusional iron intake, current iron burden and whether the goal is to decrease or maintain body iron levels. Doses of >30 mg/kg/day have been shown to be effective with a safety profile consistent with that observed at doses <30 mg/kg/day. Recent data have highlighted the ability of deferasirox to decrease cardiac iron levels and to prevent the accumulation of iron in the heart. The long-term efficacy and safety of deferasirox for up to 5 years of treatment have now been established. The availability of this effective and generally well tolerated oral therapy represents a significant advance in the management of transfusional iron overload. Keywords: deferasirox, Exjade, oral, iron chelation, iron overload, cardiac iron 

  13. Mechanisms of iron sensing and regulation in the yeast Saccharomyces cerevisiae.

    Science.gov (United States)

    Martínez-Pastor, María Teresa; Perea-García, Ana; Puig, Sergi

    2017-04-01

    Iron is a redox active element that functions as an essential cofactor in multiple metabolic pathways, including respiration, DNA synthesis and translation. While indispensable for eukaryotic life, excess iron can lead to oxidative damage of macromolecules. Therefore, living organisms have developed sophisticated strategies to optimally regulate iron acquisition, storage and utilization in response to fluctuations in environmental iron bioavailability. In the yeast Saccharomyces cerevisiae, transcription factors Aft1/Aft2 and Yap5 regulate iron metabolism in response to low and high iron levels, respectively. In addition to producing and assembling iron cofactors, mitochondrial iron-sulfur (Fe/S) cluster biogenesis has emerged as a central player in iron sensing. A mitochondrial signal derived from Fe/S synthesis is exported and converted into an Fe/S cluster that interacts directly with Aft1/Aft2 and Yap5 proteins to regulate their transcriptional function. Various conserved proteins, such as ABC mitochondrial transporter Atm1 and, for Aft1/Aft2, monothiol glutaredoxins Grx3 and Grx4 are implicated in this iron-signaling pathway. The analysis of a wide range of S. cerevisiae strains of different geographical origins and sources has shown that yeast strains adapted to high iron display growth defects under iron-deficient conditions, and highlighted connections that exist in the response to both opposite conditions. Changes in iron accumulation and gene expression profiles suggest differences in the regulation of iron homeostasis genes.

  14. Hyperspectral fluorescence imaging for cellular iron mapping in the in vitro model of Parkinson's disease

    Science.gov (United States)

    Oh, Eung Seok; Heo, Chaejeong; Kim, Ji Seon; Suh, Minah; Lee, Young Hee; Kim, Jong-Min

    2014-05-01

    Parkinson's disease (PD) is characterized by progressive dopaminergic cell loss in the substantia nigra (SN) and elevated iron levels demonstrated by autopsy. Direct visualization of iron with live imaging techniques has not yet been successful. The aim of this study is to visualize and quantify the distribution of cellular iron using an intrinsic iron hyperspectral fluorescence signal. The 1-methyl-4-phenylpyridinium (MPP+)-induced cellular model of PD was established in SHSY5Y cells exposed to iron with ferric ammonium citrate (FAC, 100 μM). The hyperspectral fluorescence signal of iron was examined using a high-resolution dark-field optical microscope system with signal absorption for the visible/near infrared spectral range. The 6-h group showed heavy cellular iron deposition compared with the 1-h group. The cellular iron was dispersed in a small particulate form, whereas the extracellular iron was aggregated. In addition, iron particles were found to be concentrated on the cell membrane/edge of shrunken cells. The iron accumulation readily occurred in MPP+-induced cells, which is consistent with previous studies demonstrating elevated iron levels in the SN. This direct iron imaging could be applied to analyze the physiological role of iron, and its application might be expanded to various neurological disorders involving metals, such as copper, manganese, or zinc.

  15. Two-Phase Accumulator

    Science.gov (United States)

    Kalb, Charles E.; Kosson, Robert L.; Alario, Joseph P.; Brown, Richard F.; Edlestein, Fred

    1990-01-01

    Two-phase accumulator maintains pressure and temperature in thermal-bus system within predetermined range during variations in heat load on system. Stores liquid and vapor ammonia. Exchanges liquid ammonia with condenser to adjust level of liquid in condenser. Prototype has capacity of 13 gallons (49 liters). Simple and highly reliable. Responds quickly, restoring pressure and temperature to proper values within minutes. Low in cost and requires little further development. Used to dispose of waste heat, such as that from electronic equipment or power-plant.

  16. Iron homeostasis: An anthropocentric perspective.

    Science.gov (United States)

    Coffey, Richard; Ganz, Tomas

    2017-08-04

    The regulation of iron metabolism in biological systems centers on providing adequate iron for cellular function while limiting iron toxicity. Because mammals cannot excrete iron, mechanisms have evolved to control iron acquisition, storage, and distribution at both systemic and cellular levels. Hepcidin, the master regulator of iron homeostasis, controls iron flows into plasma through inhibition of the only known mammalian cellular iron exporter ferroportin. Hepcidin is feedback-regulated by iron status and strongly modulated by inflammation and erythropoietic demand. This review highlights recent advances that have changed our understanding of iron metabolism and its regulation. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  17. Intravenous iron dextran for severe refractory restless legs syndrome.

    Science.gov (United States)

    Ondo, William G

    2010-05-01

    Reduced brain iron is strongly associated with restless legs syndrome (RLS). Oral iron supplements are commonly recommended for RLS but are largely ineffective due to poor absorption and poor tolerability at required doses. Intravenous iron dextran has been shown to increase brain iron content. Surprisingly only a few reports have ever presented data on the clinical effect of high dose intravenous iron for RLS. We retrospectively identified 25 subjects (age 53.2+/-11.9, 7 male) that received intravenous iron for RLS refractory to conventional treatments. We infused 1g of high molecular weight iron dextran over five hours. The age of RLS onset was 32.6+/-13.0 years and 15 subjects had a positive family history of RLS. Patients attempted 7.5+/-2.7 medications for RLS prior to iron therapy. Baseline ferritins ranged from 5 to 248 ng/ml (mean 43.5+/-58.0) and 20/25 had ferritins of less than 50. Two subjects did not complete their entire infusion due to anaphylactic type symptoms but are included. Overall, 2 subjects reported complete amelioration of all RLS symptoms, 11 reported marked improvement, 2 moderate improvement, 3 mild improvement, and 6 reported no improvement. For those with improvement, the duration of effect was highly variable (mean 15.8+/-17.7 weeks, range 1-60 weeks). Twelve subjects had multiple infusions. Iron dextran can dramatically improve refractory RLS but results are inconsistent and not predicted by patient demographics. Although burdened by a higher rate of anaphylactic reactions, iron dextran may be superior to other IV iron preparations. Copyright 2010 Elsevier B.V. All rights reserved.

  18. Excess iron: considerations related to development and early growth.

    Science.gov (United States)

    Wessling-Resnick, Marianne

    2017-12-01

    What effects might arise from early life exposures to high iron? This review considers the specific effects of high iron on the brain, stem cells, and the process of erythropoiesis and identifies gaps in our knowledge of what molecular damage may be incurred by oxidative stress that is imparted by high iron status in early life. Specific areas to enhance research on this topic include the following: longitudinal behavioral studies of children to test associations between iron exposures and mood, emotion, cognition, and memory; animal studies to determine epigenetic changes that reprogram brain development and metabolic changes in early life that could be followed through the life course; and the establishment of human epigenetic markers of iron exposures and oxidative stress that could be monitored for early origins of adult chronic diseases. In addition, efforts to understand how iron exposure influences stem cell biology could be enhanced by establishing platforms to collect biological specimens, including umbilical cord blood and amniotic fluid, to be made available to the research community. At the molecular level, there is a need to better understand stress erythropoiesis and changes in iron metabolism during pregnancy and development, especially with respect to regulatory control under high iron conditions that might promote ineffective erythropoiesis and iron-loading anemia. These investigations should focus not only on factors such as hepcidin and erythroferrone but should also include newly identified interactions between transferrin receptor-2 and the erythropoietin receptor. Finally, despite our understanding that several key micronutrients (e.g., vitamin A, copper, manganese, and zinc) support iron's function in erythropoiesis, how these nutrients interact remains, to our knowledge, unknown. It is necessary to consider many factors when formulating recommendations on iron supplementation. © 2017 American Society for Nutrition.

  19. Engineered nanoparticles. How brain friendly is this new guest?

    Science.gov (United States)

    Cupaioli, Francesca A; Zucca, Fabio A; Boraschi, Diana; Zecca, Luigi

    2014-01-01

    In the last 30 years, the use of engineered nanoparticles (NPs) has progressively increased in many industrial and medical applications. In therapy, NPs may allow more effective cellular and subcellular targeting of drugs. In diagnostic applications, quantum dots are exploited for their optical characteristics, while superparamagnetic iron oxides NPs are used in magnetic resonance imaging. NPs are used in semiconductors, packaging, textiles, solar cells, batteries and plastic materials. Despite the great progress in nanotechnologies, comparatively little is known to date on the effects that exposure to NPs may have on the human body, in general and specifically on the brain. NPs can enter the human body through skin, digestive tract, airways and blood and they may cross the blood-brain barrier to reach the central nervous system. In addition to the paucity of studies describing NP effects on brain function, some of them also suffer of insufficient NPs characterization, inadequate standardization of conditions and lack of contaminant evaluation, so that results from different studies can hardly be compared. It has been shown in vitro and in vivo in rodents that NPs can impair dopaminergic and serotoninergic systems. Changes of neuronal morphology and neuronal death were reported in mice treated with NPs. NPs can also affect the respiratory chain of mitochondria and Bax protein levels, thereby causing apoptosis. Changes in expression of genes involved in redox pathways in mouse brain regions were described. NPs can induce autophagy, and accumulate in lysosomes impairing their degradation capacity. Cytoskeleton and vesicle trafficking may also be affected. NPs treated animals showed neuroinflammation with microglia activation, which could induce neurodegeneration. Considering the available data, it is important to design adequate models and experimental systems to evaluate in a reliable and controlled fashion the effects of NPs on the brain, and generate data

  20. Mitochondrial dysfunction may explain the cardiomyopathy of chronic iron overload.

    Science.gov (United States)

    Gao, Xueshan; Qian, Mingwei; Campian, Jian Li; Marshall, James; Zhou, Zhanxiang; Roberts, Andrew M; Kang, Y James; Prabhu, Sumanth D; Sun, Xiao-Feng; Eaton, John W

    2010-08-01

    In patients with hemochromatosis, cardiac dysfunction may appear years after they have reached a state of iron overload. We hypothesized that cumulative iron-catalyzed oxidant damage to mitochondrial DNA (mtDNA) might explain the cardiomyopathy of chronic iron overload. Mice were given repetitive injections of iron dextran for a total of 4weeks after which the iron-loaded mice had elevated cardiac iron, modest cardiac hypertrophy, and cardiac dysfunction. qPCR amplification of near-full-length ( approximately 16kb) mtDNA revealed >50% loss of full-length product, whereas amounts of a qPCR product of a nuclear gene (13kb region of beta globin) were unaffected. Quantitative rtPCR analyses revealed 60-70% loss of mRNA for proteins encoded by mtDNA with no change in mRNA abundance for nuclear-encoded respiratory subunits. These changes coincided with proportionate reductions in complex I and IV activities and decreased respiration of isolated cardiac mitochondria. We conclude that chronic iron overload leads to cumulative iron-mediated damage to mtDNA and impaired synthesis of mitochondrial respiratory chain subunits. The resulting respiratory dysfunction may explain the slow development of cardiomyopathy in chronic iron overload and similar accumulation of damage to mtDNA may also explain the mitochondrial dysfunction observed in slowly progressing diseases such as neurodegenerative disorders. Copyright 2010 Elsevier Inc. All rights reserved.

  1. Iron fortification of banana by the expression of soybean ferritin.

    Science.gov (United States)

    Kumar, Gujulla B Sunil; Srinivas, Lingam; Ganapathi, Thumballi Ramabhatta

    2011-08-01

    Iron deficiency anemia is one of the serious ailments related to nutrition in the developing countries. Fruit and vegetable crops favor the bioavailability of iron. Banana is consumed as a staple food in the tropics. Iron-fortified bananas provide an effective means of controlling the iron deficiency. Embryogenic cells of banana cv. Rasthali (AAB) were transformed with soybean ferritin cDNA using two different expression cassettes pSF and pEFE-SF to express ferritin. Transgenic nature of the regenerated plants was confirmed by PCR. Transgenic plants were regenerated and analyzed through PCR and PCR-Southern analysis. The expression of ferritin was confirmed by RT-PCR. Iron and zinc levels in the transgenic and control plants were estimated by atomic absorption spectroscopy. A 6.32-fold increase in iron accumulation and a 4.58-fold increase in the zinc levels were noted in the leaves of transgenic plants. Thus, iron- and zinc-fortified bananas could be developed as a functional food to overcome the malnutrition-related iron deficiency. This is the first report on the iron and zinc fortification of banana.

  2. Acetate, lactate, propionate, and isobutyrate as electron donors for iron and sulfate reduction in Arctic marine sediments, Svalbard

    DEFF Research Database (Denmark)

    Finke, Niko; Vandieken, Verona; Jørgensen, Bo Barker

    2007-01-01

    . Inhibition of sulfate reduction with selenate resulted in the accumulation of acetate, propionate, and isobutyrate. The acetate turnover rates determined by radiotracer and accumulation after inhibition were similar. VFA turnover accounted for 21% and 52% of the mineralization through sulfate reduction...... by alternative e--donors. The accumulation of VFA in the selenate-inhibited 0-2 cm slurry did not enhance iron reduction, indicating that iron reducers were not limited by VFA availability....

  3. [A case of cerebellar degeneration with schizophrenia-like psychosis, severe iron deficiency, hypoceruloplasminemia and abnormal electroretinography: a new syndrome?].

    Science.gov (United States)

    Kimura, A; Yoshino, H; Yuasa, T

    2001-08-01

    A 33-year-old male patient began to develop schizophrenia-like symptoms and slowly progressive cerebellar ataxia. He was 170 cm tall and he had mild frontal baldness. Psychiatrically he was aconative, only willing to do nothing all day long after admission. He had neither hallucinations nor delusions, and his mental acuity was normal. Neurological examination revealed positive cerebellar signs including clumsiness in F-N-T and K-H-T and dysdiadochokinesis. He could neither stand up nor walk because of ataxia. The brain MRI showed severe cerebellar atrophy with normal basal ganglia. His EEG and the value of NCV were within normal range, whereas electroretinography showed a notable abnormality, pointing to the extremely small b-wave, resulting in a negative shape of the ERG. Although he was eating sufficiently, the level of serum iron and ferritin remained constantly low. The serum copper level was within normal range, whereas the serum ceruloplasmin level was mildly decreased. A hepatic biopsy indicated no accumulation of copper or iron. This case suggests the importance of the investigation of the serum iron and ceruloplasmin levels in patients who have cerebellar degeneration with psychosis.

  4. Endoplasmic reticulum-mitochondria junction is required for iron homeostasis.

    Science.gov (United States)

    Xue, Yong; Schmollinger, Stefan; Attar, Narsis; Campos, Oscar A; Vogelauer, Maria; Carey, Michael F; Merchant, Sabeeha S; Kurdistani, Siavash K

    2017-08-11

    The endoplasmic reticulum (ER)-mitochondria encounter structure (ERMES) is a protein complex that physically tethers the two organelles to each other and creates the physical basis for communication between them. ERMES functions in lipid exchange between the ER and mitochondria, protein import into mitochondria, and maintenance of mitochondrial morphology and genome. Here, we report that ERMES is also required for iron homeostasis. Loss of ERMES components activates an Aft1-dependent iron deficiency response even in iron-replete conditions, leading to accumulation of excess iron inside the cell. This function is independent of known ERMES roles in calcium regulation, phospholipid biosynthesis, or effects on mitochondrial morphology. A mutation in the vacuolar protein sorting 13 ( VPS13 ) gene that rescues the glycolytic phenotype of ERMES mutants suppresses the iron deficiency response and iron accumulation. Our findings reveal that proper communication between the ER and mitochondria is required for appropriate maintenance of cellular iron levels. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  5. Haemosiderin deposition in Donkey (Equus asinus) livers: Comparison of quantitative histochemistry for iron and liver iron content.

    Science.gov (United States)

    Brown, P J; Whitbread, T J; Burden, F A; Bailey, M; Carley, K; Daniell, L; Jones, C; Bell, N J

    2011-04-01

    Post mortem liver samples from 12 donkeys (Equus asinus) aged 21-57 years (4 females, 1 stallion, 7 geldings), were assessed chemically for copper and iron content on a wet weight basis and histologically for stainable iron. Chemical liver copper content ranged from 2.7 to 4.8μg/g (mean 3.5±0.05μg/g). Chemical liver iron content ranged from 524 to 5010μg/g (mean 1723±1258μg/g). Histochemical iron was measured morphometrically using a computer-based image analysis system; percentage section area staining for iron ranged from 0.84% to 26.69% (mean 10.82±8.36%). There was no clear correlation, within the wide range of iron values, between histochemically demonstrable iron and chemically measured iron content. No clear age-related increase was apparent for either parameter in these aged donkeys. The accumulation of iron in the liver of donkeys may represent a physiological haemosiderosis rather than pathological haemochromatosis. Copyright © 2010 Elsevier Ltd. All rights reserved.

  6. Micronutrient Accumulation in Conilon Coffee Berries with Different Maturation Cycles

    Directory of Open Access Journals (Sweden)

    Wellington Braida Marré

    2015-10-01

    Full Text Available ABSTRACT The number of days between anthesis and maturation of conilon coffee berries varies according to the genotype. Thus, it is believed that periods of greater nutrient demand for fruit formation also vary according to the genotype, directly influencing fertilizer management. The goal of this study was to establish accumulation curves for the micronutrients boron, copper, iron, manganese, and zinc in conilon coffee trees with different maturation cycles. The experiment was conducted in Nova Venécia, State of Espírito Santo, Brazil, during the reproductive cycle of the 2010/2011 crop year. Four coffee genotypes with different maturation cycles (early, intermediate, late, and super-late were studied. A completely randomized experimental design was used with five replications. The treatments correspond to the accumulation of B, Cu, Fe, Mn, and Zn in the berries every 28 days in the period from flowering to harvest. The early, intermediate, and late genotypes accumulated Fe, Cu, and Mn in a similar manner, with sigmoid curves, whereas the super-late genotype accumulated these nutrients exponentially. Zn was accumulated by all four genotypes following a sigmoid curve. The early, intermediate, and late genotypes accumulated B linearly, whereas the super-late genotype accumulated B following a sigmoid curve. The maturation cycle of the genotype must be taken into account to apply the correct rate of micronutrient fertilization in coffee plantations.

  7. Recent advances in the understanding of iron overload in sideroblastic myelodysplastic syndrome.

    NARCIS (Netherlands)

    Cuijpers, M.L.H.; Raymakers, R.A.P.; Mackenzie, M.W.; Witte, T.J.M. de; Swinkels, D.W.

    2010-01-01

    Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal haematopoietic stem cell malignancies. A subgroup, the so-called sideroblastic MDS, shows ring sideroblasts in the bone marrow aspirate that represent mitochondrial iron accumulation. Patients with sideroblastic MDS also develop

  8. Brain herniation

    Science.gov (United States)

    ... herniation; Uncal herniation; Subfalcine herniation; Tonsillar herniation; Herniation - brain ... Brain herniation occurs when something inside the skull produces pressure that moves brain tissues. This is most ...

  9. The aeolian dust accumulation curve

    NARCIS (Netherlands)

    Goossens, D.

    2001-01-01

    This article presents a simple physical concept of aeolian dust accumulation, based on the behaviour of the subprocesses of dust deposition and dust erosion. The concept is tested in an aeolian dust wind tunnel. The agreement between the accumulation curve predicted by the model and the accumulation

  10. Magnetic studies of iron-entities in human tissues

    Energy Technology Data Exchange (ETDEWEB)

    Slawska-Waniewska, A. E-mail: slaws@ifpan.edu.pl; Mosiniewicz-Szablewska, E.; Nedelko, N.; Galazka-Friedman, J.; Friedman, A

    2004-05-01

    Iron-entities in the human liver, brain and blood tissues have been investigated by means of EPR spectroscopy and magnetization measurements over the temperature range 4-300 K. The identification of the most typical forms of iron in the human body (i.e. isolated Fe-ions bonded in hemoglobin and transferrin as well as exchange coupled Fe-ions in nanosized ferritin cores) is presented.

  11. Mineralogy and geochemistry of banded iron formation and iron ...

    Indian Academy of Sciences (India)

    The geological complexities of banded iron formation (BIF) and associated iron ores of Jilling–Langalata iron ore deposits, Singhbhum–North Orissa Craton, belonging to Iron Ore Group (IOG) eastern India have been studied in detail along with the geochemical evaluation of different iron ores. The geochemical and ...

  12. Liver Iron Contents in Rats after Administration of Certain Iron ...

    African Journals Online (AJOL)

    Liver Iron Contents in Rats after Administration of Certain Iron Compounds. CP van Wyk, DJ Robbins. Abstract. The effect of consumption of certain iron compounds on liver iron deposition was studied in rats, in each case at 4 dietary iron levels ranging from 70 to 206 mg/100 g diet. In one of two series the basic diet was ...