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James Connor

TitleProfessor
InstitutionCollege of Medicine
DepartmentNeurosurgery
Address500 University Drive Hershey PA 17033
Mailbox: H110
Phone7175314541

 Overview 
 overview
PREFERRED TITLE/ROLE:



Distinguished Professor of Neurosurgery, Neural and Behavioral Sciences and Pediatrics

Vice Chair of Neurosurgery Research

Director, Center for Aging and Neurodegenerative Diseases



SECONDARY APPOINTMENT(S)/ INSTITUTE(S)/ CENTER(S):



Neuroscience Institute



GRADUATE PROGRAM AFFILIATIONS:



Anatomy, Cell and Molecular Biology, Integrative Biosciences, MD/PhD Degree Program, Neuroscience, Nutrition



EDUCATION:



Ph.D., University of California, Berkeley, 1981

Postdoctoral Training, Boston University School of Medicine, 1981-1983



NARRATIVE:



The projects in my laboratory are designed to understand the cellular and molecular mechanisms by which cells regulate their iron status. Iron is essential for normal function but at the same time too much iron can be toxic. Therefore cells have an exquisite system for regulating iron levels. When these regulatory mechanims become dysfunctional either through damage, disease or genetic modification cell behavior is abnormal and they sometimes die. Iron imbalance is associated with a prooxidative stress and a proinflammatory environment. Much of our work has focused on mechanisms responsible for regulating iron in the brain. One basic function in which iron is required in the brain is for the production of myelin. We have shown that too little iron during perinatal development will result in hypomyelination. We have also provided evidence that iron can contribute to Multiple Sclerosis (MS). We have established that there is too much iron in the brain in a number of neurological disorders including Alzheimer's (AD) and Parkinson's Diseases (PD). In contrast, there appears to be too little iron in the brain in a disorder known as Restless Legs Syndrome. What is clear from our studies is that optimal brain function requires a tightly regulated iron supply and that the iron must be delivered in a timely manner. To determine the mechanism(s) for brain iron delivery and the regulation of those mechanisms we have focused on a number of mouse and rat mutants as a model of human diseases in which the ability to acquire, moblize or store iron has been disrupted. In the context of these studies we have generated a very promising mouse line in which the gene for the iron storage protein, ferritin, has been deleted. This model is helping to understand the contribution of loss of brain iron homeostatic mechanisms to those changes seen in the brain with AD, PD and MS. In the course of these studies on ferritin, we found that in addition to the cytoplasmic location, ferritin can be found in cell nuclei under some conditions. This observation has led us to basic molecular studies on DNA binding and protection as well as intracellular trafficking of ferritin. The evidence strongly indicates that nuclear ferritin is associated with tumorigenesis. Another avenue under exploration in the context of homeostatic mechanisms is the analysis of gene mutations that lead to disruption of iron status. We have identified mutations in the Hfe gene as a risk factor for Alzheimer's Disease and Amyotrophic Lateral Sclerosis (Lou Gehrig's Disease). The Hfe protein is thought to limit iron uptake by cells and a mutation in this protein may promote inflammation and oxidative stress. We also have a line of research aimed at understanding mechanisms of iron uptake into the brain. This line of research should provide insight into how too much iron can enter the brain in disease states. These studies have led to one particularly novel and important finding of a new receptor in the brain for ferritin. This receptor is expressed only by oligodendrocytes in the brain. We are investigating the possibility that the selective expression of ferritin receptors on oligodendrocytes may have medically important implications for Multiple Sclerosis.



In regard to function of iron in the brain, one area of focus is the regulation of those proteins responsible for iron management in cells. The iron management proteins are regulated by cytoplasmic mRNA binding proteins that are known are iron regulatory proteins. Our project is to determine how the cytoplasmic mRNA binding proteins find their target mRNAs. The outcome of these studies may help us understand how a cell can become iron overloaded but also will contribute significantly to our general knowledge of post-transcriptional gene regulation. One additional approach which is aimed at understanding the function of iron in cells is gene expression profiling. In these studies we have asked the question: "what does it mean to a cell at the molecular level to be iron loaded or iron starved". So far, we have identified a dozen novel genes and a number of genes not previously known to be iron responsive. These data are relevant to cancer and Alzheimer's Disease and Restless Legs Syndrome.



Finally, to examine the consequences of iron mismanagement in the brain, we utilize both cell culture and animal models. The cell culture model seeks to identify the intracellular events associated with iron induced stress and uses state of the art microscopic and flurimetric techniques. Sara Robb received the Marian Kies Award from the American Society of Neurochemistry for outstanding graduate research for developing this model in my laboratory.


 Bibliographic 
 selected publications
Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Faculty can login to make corrections and additions.
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  1. Alkhateeb AA, Connor JR. The significance of ferritin in cancer: Anti-oxidation, inflammation and tumorigenesis. Biochim Biophys Acta. 2013 Dec; 1836(2):245-54.
    View in: PubMed
  2. Dellinger A, Zhou Z, Connor J, Madhankumar AB, Pamujula S, Sayes CM, Kepley CL. Application of fullerenes in nanomedicine: an update. Nanomedicine (Lond). 2013 Jul; 8(7):1191-208.
    View in: PubMed
  3. Su XW, Lee SY, Mitchell RM, Stephens HE, Simmons Z, Connor JR. H63D HFE polymorphisms are associated with increased disease duration and decreased muscle superoxide dismutase-1 expression in amyotrophic lateral sclerosis patients. Muscle Nerve. 2013 Aug; 48(2):242-6.
    View in: PubMed
  4. Patton SM, Cho YW, Clardy TW, Allen RP, Earley CJ, Connor JR. Proteomic analysis of the cerebrospinal fluid of patients with restless legs syndrome/Willis-Ekbom disease. Fluids Barriers CNS. 2013; 10(1):20.
    View in: PubMed
  5. Nandar W, Neely EB, Unger E, Connor JR. A mutation in the HFE gene is associated with altered brain iron profiles and increased oxidative stress in mice. Biochim Biophys Acta. 2013 Jun; 1832(6):729-41.
    View in: PubMed
  6. Alkhateeb AA, Han B, Connor JR. Ferritin stimulates breast cancer cells through an iron-independent mechanism and is localized within tumor-associated macrophages. Breast Cancer Res Treat. 2013 Feb; 137(3):733-44.
    View in: PubMed
  7. Alkhateeb AA, Leitzel K, Ali SM, Campbell-Baird C, Evans M, Fuchs EM, Köstler WJ, Lipton A, Connor J. Elevation in inflammatory serum biomarkers predicts response to trastuzumab-containing therapy. PLoS One. 2012; 7(12):e51379.
    View in: PubMed
  8. Rao R, Tkac I, Unger EL, Ennis K, Hurst A, Schallert T, Connor J, Felt B, Georgieff MK. Iron supplementation dose for perinatal iron deficiency differentially alters the neurochemistry of the frontal cortex and hippocampus in adult rats. Pediatr Res. 2013 Jan; 73(1):31-7.
    View in: PubMed
  9. Patton SM, Coe CL, Lubach GR, Connor JR. Quantitative proteomic analyses of cerebrospinal fluid using iTRAQ in a primate model of iron deficiency anemia. Dev Neurosci. 2012; 34(4):354-65.
    View in: PubMed
  10. Unger EL, Hurst AR, Georgieff MK, Schallert T, Rao R, Connor JR, Kaciroti N, Lozoff B, Felt B. Behavior and monoamine deficits in prenatal and perinatal iron deficiency are not corrected by early postnatal moderate-iron or high-iron diets in rats. J Nutr. 2012 Nov; 142(11):2040-9.
    View in: PubMed
  11. Mazanov J, Huybers T, Connor J. Prioritising health in anti-doping: what Australians think. J Sci Med Sport. 2012 Sep; 15(5):381-5.
    View in: PubMed
  12. Liu Y, Connor JR. Iron and ER stress in neurodegenerative disease. Biometals. 2012 Aug; 25(4):837-45.
    View in: PubMed
  13. Carkaci-Salli N, Battula S, Wang X, Connor JR, Vrana KE. Gender-specific regulation of tyrosine hydroxylase in thymocyte differentiation antigen-1 knockout mice. J Neurosci Res. 2012 Aug; 90(8):1583-8.
    View in: PubMed
  14. Wang J, Shaffer ML, Eslinger PJ, Sun X, Weitekamp CW, Patel MM, Dossick D, Gill DJ, Connor JR, Yang QX. Maturational and aging effects on human brain apparent transverse relaxation. PLoS One. 2012; 7(2):e31907.
    View in: PubMed
  15. Otto M, Bowser R, Turner M, Berry J, Brettschneider J, Connor J, Costa J, Cudkowicz M, Glass J, Jahn O, Lehnert S, Malaspina A, Parnetti L, Petzold A, Shaw P, Sherman A, Steinacker P, Süssmuth S, Teunissen C, Tumani H, Wuolikainen A, Ludolph A. Roadmap and standard operating procedures for biobanking and discovery of neurochemical markers in ALS. Amyotroph Lateral Scler. 2012 Jan; 13(1):1-10.
    View in: PubMed
  16. Leitner DF, Connor JR. Functional roles of transferrin in the brain. Biochim Biophys Acta. 2012 Mar; 1820(3):393-402.
    View in: PubMed
  17. Mairuae N, Connor JR, Cheepsunthorn P. Increased cellular iron levels affect matrix metalloproteinase expression and phagocytosis in activated microglia. Neurosci Lett. 2011 Aug 1; 500(1):36-40.
    View in: PubMed
  18. Connor JR, Ponnuru P, Lee BY, Podskalny GD, Alam S, Allen RP, Earley CJ, Yang QX. Postmortem and imaging based analyses reveal CNS decreased myelination in restless legs syndrome. Sleep Med. 2011 Jun; 12(6):614-9.
    View in: PubMed
  19. Lee SY, Liu S, Mitchell RM, Slagle-Webb B, Hong YS, Sheehan JM, Connor JR. HFE polymorphisms influence the response to chemotherapeutic agents via induction of p16INK4A. Int J Cancer. 2011 Nov 1; 129(9):2104-14.
    View in: PubMed
  20. Patton SM, Ponnuru P, Snyder AM, Podskalny GD, Connor JR. Hypoxia-inducible factor pathway activation in restless legs syndrome patients. Eur J Neurol. 2011 Nov; 18(11):1329-35.
    View in: PubMed
  21. Todorich B, Zhang X, Connor JR. H-ferritin is the major source of iron for oligodendrocytes. Glia. 2011 Jun; 59(6):927-35.
    View in: PubMed
  22. Connor JR, Ponnuru P, Wang XS, Patton SM, Allen RP, Earley CJ. Profile of altered brain iron acquisition in restless legs syndrome. Brain. 2011 Apr; 134(Pt 4):959-68.
    View in: PubMed
  23. Bartzokis G, Lu PH, Tingus K, Peters DG, Amar CP, Tishler TA, Finn JP, Villablanca P, Altshuler LL, Mintz J, Neely E, Connor JR. Gender and iron genes may modify associations between brain iron and memory in healthy aging. Neuropsychopharmacology. 2011 Jun; 36(7):1375-84.
    View in: PubMed
  24. Liu X, Madhankumar AB, Slagle-Webb B, Sheehan JM, Surguladze N, Connor JR. Heavy chain ferritin siRNA delivered by cationic liposomes increases sensitivity of cancer cells to chemotherapeutic agents. Cancer Res. 2011 Mar 15; 71(6):2240-9.
    View in: PubMed
  25. Weston CL, Glantz MJ, Connor JR. Detection of cancer cells in the cerebrospinal fluid: current methods and future directions. Fluids Barriers CNS. 2011; 8(1):14.
    View in: PubMed
  26. Liu Y, Lee SY, Neely E, Nandar W, Moyo M, Simmons Z, Connor JR. Mutant HFE H63D protein is associated with prolonged endoplasmic reticulum stress and increased neuronal vulnerability. J Biol Chem. 2011 Apr 15; 286(15):13161-70.
    View in: PubMed
  27. Nandar W, Connor JR. HFE gene variants affect iron in the brain. J Nutr. 2011 Apr 1; 141(4):729S-739S.
    View in: PubMed
  28. Ali-Rahmani F, Hengst JA, Connor JR, Schengrund CL. Effect of HFE variants on sphingolipid expression by SH-SY5Y human neuroblastoma cells. Neurochem Res. 2011 Sep; 36(9):1687-96.
    View in: PubMed
  29. Hadziahmetovic M, Song Y, Ponnuru P, Iacovelli J, Hunter A, Haddad N, Beard J, Connor JR, Vaulont S, Dunaief JL. Age-dependent retinal iron accumulation and degeneration in hepcidin knockout mice. Invest Ophthalmol Vis Sci. 2011 Jan; 52(1):109-18.
    View in: PubMed
  30. Radenahmad N, Saleh F, Sawangjaroen K, Vongvatcharanon U, Subhadhirasakul P, Rundorn W, Withyachumnarnkul B, Connor JR. Young coconut juice, a potential therapeutic agent that could significantly reduce some pathologies associated with Alzheimer's disease: novel findings. Br J Nutr. 2011 Mar; 105(5):738-46.
    View in: PubMed
  31. Snyder AM, Neely EB, Levi S, Arosio P, Connor JR. Regional and cellular distribution of mitochondrial ferritin in the mouse brain. J Neurosci Res. 2010 Nov 1; 88(14):3133-43.
    View in: PubMed
  32. Mairuae N, Hall Ii EC, Cheepsunthorn P, Lee SY, Connor JR. The H63D HFE gene variant promotes activation of the intrinsic apoptotic pathway via mitochondria dysfunction following ß-amyloid peptide exposure. J Neurosci Res. 2010 Nov 1; 88(14):3079-89.
    View in: PubMed
  33. Wang J, Eslinger PJ, Doty RL, Zimmerman EK, Grunfeld R, Sun X, Meadowcroft MD, Connor JR, Price JL, Smith MB, Yang QX. Olfactory deficit detected by fMRI in early Alzheimer's disease. Brain Res. 2010 Oct 21; 1357:184-94.
    View in: PubMed
  34. Mitchell RM, Simmons Z, Beard JL, Stephens HE, Connor JR. Plasma biomarkers associated with ALS and their relationship to iron homeostasis. Muscle Nerve. 2010 Jul; 42(1):95-103.
    View in: PubMed
  35. Aschner M, Levin ED, Suñol C, Olopade JO, Helmcke KJ, Avila DS, Sledge D, Ali RH, Upchurch L, Donerly S, Linney E, Forsby A, Ponnuru P, Connor JR. Gene-environment interactions: neurodegeneration in non-mammals and mammals. Neurotoxicology. 2010 Sep; 31(5):582-8.
    View in: PubMed
  36. Alkhateeb AA, Connor JR. Nuclear ferritin: A new role for ferritin in cell biology. Biochim Biophys Acta. 2010 Aug; 1800(8):793-7.
    View in: PubMed
  37. Todorich B, Olopade JO, Surguladze N, Zhang X, Neely E, Connor JR. The mechanism of vanadium-mediated developmental hypomyelination is related to destruction of oligodendrocyte progenitors through a relationship with ferritin and iron. Neurotox Res. 2011 Apr; 19(3):361-73.
    View in: PubMed
  38. McEchron MD, Alexander DN, Smith ME, Hoffman DL, Podskalny GD, Connor JR. Altered eyeblink reflex conditioning in restless legs syndrome patients. Sleep Med. 2010 Mar; 11(3):314-9.
    View in: PubMed
  39. Hall EC, Lee SY, Simmons Z, Neely EB, Nandar W, Connor JR. Prolyl-peptidyl isomerase, Pin1, phosphorylation is compromised in association with the expression of the HFE polymorphic allele, H63D. Biochim Biophys Acta. 2010 Apr; 1802(4):389-95.
    View in: PubMed
  40. Bartzokis G, Lu PH, Tishler TA, Peters DG, Kosenko A, Barrall KA, Finn JP, Villablanca P, Laub G, Altshuler LL, Geschwind DH, Mintz J, Neely E, Connor JR. Prevalent iron metabolism gene variants associated with increased brain ferritin iron in healthy older men. J Alzheimers Dis. 2010; 20(1):333-41.
    View in: PubMed
  41. Snyder AM, Wang X, Patton SM, Arosio P, Levi S, Earley CJ, Allen RP, Connor JR. Mitochondrial ferritin in the substantia nigra in restless legs syndrome. J Neuropathol Exp Neurol. 2009 Nov; 68(11):1193-9.
    View in: PubMed
  42. Hall EC, Lee SY, Mairuae N, Simmons Z, Connor JR. Expression of the HFE allelic variant H63D in SH-SY5Y cells affects tau phosphorylation at serine residues. Neurobiol Aging. 2011 Aug; 32(8):1409-19.
    View in: PubMed
  43. Connor JR, Ghio AJ. The impact of host iron homeostasis on disease. Preface. Biochim Biophys Acta. 2009 Jul; 1790(7):581-2.
    View in: PubMed
  44. Mitchell RM, Lee SY, Simmons Z, Connor JR. HFE polymorphisms affect cellular glutamate regulation. Neurobiol Aging. 2011 Jun; 32(6):1114-23.
    View in: PubMed
  45. Connor JR, Wang XS, Allen RP, Beard JL, Wiesinger JA, Felt BT, Earley CJ. Altered dopaminergic profile in the putamen and substantia nigra in restless leg syndrome. Brain. 2009 Sep; 132(Pt 9):2403-12.
    View in: PubMed
  46. Meadowcroft MD, Connor JR, Smith MB, Yang QX. MRI and histological analysis of beta-amyloid plaques in both human Alzheimer's disease and APP/PS1 transgenic mice. J Magn Reson Imaging. 2009 May; 29(5):997-1007.
    View in: PubMed
  47. Todorich B, Pasquini JM, Garcia CI, Paez PM, Connor JR. Oligodendrocytes and myelination: the role of iron. Glia. 2009 Apr 1; 57(5):467-78.
    View in: PubMed
  48. Earley CJ, Allen RP, Connor JR, Ferrucci L, Troncoso J. The dopaminergic neurons of the A11 system in RLS autopsy brains appear normal. Sleep Med. 2009 Dec; 10(10):1155-7.
    View in: PubMed
  49. Madhankumar AB, Slagle-Webb B, Wang X, Yang QX, Antonetti DA, Miller PA, Sheehan JM, Connor JR. Efficacy of interleukin-13 receptor-targeted liposomal doxorubicin in the intracranial brain tumor model. Mol Cancer Ther. 2009 Mar; 8(3):648-54.
    View in: PubMed
  50. Mitchell RM, Lee SY, Randazzo WT, Simmons Z, Connor JR. Influence of HFE variants and cellular iron on monocyte chemoattractant protein-1. J Neuroinflammation. 2009; 6:6.
    View in: PubMed
  51. Chiò A, Schymick JC, Restagno G, Scholz SW, Lombardo F, Lai SL, Mora G, Fung HC, Britton A, Arepalli S, Gibbs JR, Nalls M, Berger S, Kwee LC, Oddone EZ, Ding J, Crews C, Rafferty I, Washecka N, Hernandez D, Ferrucci L, Bandinelli S, Guralnik J, Macciardi F, Torri F, Lupoli S, Chanock SJ, Thomas G, Hunter DJ, Gieger C, Wichmann HE, Calvo A, Mutani R, Battistini S, Giannini F, Caponnetto C, Mancardi GL, La Bella V, Valentino F, Monsurrò MR, Tedeschi G, Marinou K, Sabatelli M, Conte A, Mandrioli J, Sola P, Salvi F, Bartolomei I, Siciliano G, Carlesi C, Orrell RW, Talbot K, Simmons Z, Connor J, Pioro EP, Dunkley T, Stephan DA, Kasperaviciute D, Fisher EM, Jabonka S, Sendtner M, Beck M, Bruijn L, Rothstein J, Schmidt S, Singleton A, Hardy J, Traynor BJ. A two-stage genome-wide association study of sporadic amyotrophic lateral sclerosis. Hum Mol Genet. 2009 Apr 15; 18(8):1524-32.
    View in: PubMed
  52. Todorich B, Zhang X, Slagle-Webb B, Seaman WE, Connor JR. Tim-2 is the receptor for H-ferritin on oligodendrocytes. J Neurochem. 2008 Dec; 107(6):1495-505.
    View in: PubMed
  53. Mitchell RM, Freeman WM, Randazzo WT, Stephens HE, Beard JL, Simmons Z, Connor JR. A CSF biomarker panel for identification of patients with amyotrophic lateral sclerosis. Neurology. 2009 Jan 6; 72(1):14-9.
    View in: PubMed
  54. Connor JR, Wang XS, Neely EB, Ponnuru P, Morita H, Beard J. Comparative study of the influence of Thy1 deficiency and dietary iron deficiency on dopaminergic profiles in the mouse striatum. J Neurosci Res. 2008 Nov 1; 86(14):3194-202.
    View in: PubMed
  55. Snyder AM, Connor JR. Iron, the substantia nigra and related neurological disorders. Biochim Biophys Acta. 2009 Jul; 1790(7):606-14.
    View in: PubMed
  56. Connor JR. Pathophysiology of restless legs syndrome: evidence for iron involvement. Curr Neurol Neurosci Rep. 2008 Mar; 8(2):162-6.
    View in: PubMed
  57. Allen RP, Connor JR, Hyland K, Earley CJ. Abnormally increased CSF 3-Ortho-methyldopa (3-OMD) in untreated restless legs syndrome (RLS) patients indicates more severe disease and possibly abnormally increased dopamine synthesis. Sleep Med. 2009 Jan; 10(1):123-8.
    View in: PubMed
  58. Geguchadze RN, Coe CL, Lubach GR, Clardy TW, Beard JL, Connor JR. CSF proteomic analysis reveals persistent iron deficiency-induced alterations in non-human primate infants. J Neurochem. 2008 Apr; 105(1):127-36.
    View in: PubMed
  59. Zinnanti WJ, Lazovic J, Housman C, LaNoue K, O'Callaghan JP, Simpson I, Woontner M, Goodman SI, Connor JR, Jacobs RE, Cheng KC. Mechanism of age-dependent susceptibility and novel treatment strategy in glutaric acidemia type I. J Clin Invest. 2007 Nov; 117(11):3258-70.
    View in: PubMed
  60. Kim BH, Jun YC, Jin JK, Kim JI, Kim NH, Leibold EA, Connor JR, Choi EK, Carp RI, Kim YS. Alteration of iron regulatory proteins (IRP1 and IRP2) and ferritin in the brains of scrapie-infected mice. Neurosci Lett. 2007 Jul 18; 422(3):158-63.
    View in: PubMed
  61. Meadowcroft MD, Zhang S, Liu W, Park BS, Connor JR, Collins CM, Smith MB, Yang QX. Direct magnetic resonance imaging of histological tissue samples at 3.0T. Magn Reson Med. 2007 May; 57(5):835-41.
    View in: PubMed
  62. Fisher J, Devraj K, Ingram J, Slagle-Webb B, Madhankumar AB, Liu X, Klinger M, Simpson IA, Connor JR. Ferritin: a novel mechanism for delivery of iron to the brain and other organs. Am J Physiol Cell Physiol. 2007 Aug; 293(2):C641-9.
    View in: PubMed
  63. Ward KL, Tkac I, Jing Y, Felt B, Beard J, Connor J, Schallert T, Georgieff MK, Rao R. Gestational and lactational iron deficiency alters the developing striatal metabolome and associated behaviors in young rats. J Nutr. 2007 Apr; 137(4):1043-9.
    View in: PubMed
  64. Foglieni B, Ferrari F, Goldwurm S, Santambrogio P, Castiglioni E, Sessa M, Volontè MA, Lalli S, Galli C, Wang XS, Connor J, Sironi F, Canesi M, Biasiotto G, Pezzoli G, Levi S, Ferrari M, Arosio P, Cremonesi L. Analysis of ferritin genes in Parkinson disease. Clin Chem Lab Med. 2007; 45(11):1450-6.
    View in: PubMed
  65. House MJ, St Pierre TG, Kowdley KV, Montine T, Connor J, Beard J, Berger J, Siddaiah N, Shankland E, Jin LW. Correlation of proton transverse relaxation rates (R2) with iron concentrations in postmortem brain tissue from alzheimer's disease patients. Magn Reson Med. 2007 Jan; 57(1):172-80.
    View in: PubMed
  66. Lee SY, Patton SM, Henderson RJ, Connor JR. Consequences of expressing mutants of the hemochromatosis gene (HFE) into a human neuronal cell line lacking endogenous HFE. FASEB J. 2007 Feb; 21(2):564-76.
    View in: PubMed
  67. Wang XS, Simmons Z, Liu W, Boyer PJ, Connor JR. Differential expression of genes in amyotrophic lateral sclerosis revealed by profiling the post mortem cortex. Amyotroph Lateral Scler. 2006 Dec; 7(4):201-10.
    View in: PubMed
  68. Madhankumar AB, Slagle-Webb B, Mintz A, Sheehan JM, Connor JR. Interleukin-13 receptor-targeted nanovesicles are a potential therapy for glioblastoma multiforme. Mol Cancer Ther. 2006 Dec; 5(12):3162-9.
    View in: PubMed
  69. Zhang X, Surguladze N, Slagle-Webb B, Cozzi A, Connor JR. Cellular iron status influences the functional relationship between microglia and oligodendrocytes. Glia. 2006 Dec; 54(8):795-804.
    View in: PubMed
  70. Connor JR, Lee SY. HFE mutations and Alzheimer's disease. J Alzheimers Dis. 2006 Nov; 10(2-3):267-76.
    View in: PubMed
  71. Zinnanti WJ, Lazovic J, Wolpert EB, Antonetti DA, Smith MB, Connor JR, Woontner M, Goodman SI, Cheng KC. New insights for glutaric aciduria type I. Brain. 2006 Aug; 129(Pt 8):e55.
    View in: PubMed
  72. Ill AM, Mitchell TR, Neely EB, Connor JR. Metabolic analysis of mouse brains that have compromised iron storage. Metab Brain Dis. 2006 Sep; 21(2-3):77-87.
    View in: PubMed
  73. Clardy SL, Wang X, Boyer PJ, Earley CJ, Allen RP, Connor JR. Is ferroportin-hepcidin signaling altered in restless legs syndrome? J Neurol Sci. 2006 Sep 25; 247(2):173-9.
    View in: PubMed
  74. Felt BT, Beard JL, Schallert T, Shao J, Aldridge JW, Connor JR, Georgieff MK, Lozoff B. Persistent neurochemical and behavioral abnormalities in adulthood despite early iron supplementation for perinatal iron deficiency anemia in rats. Behav Brain Res. 2006 Aug 10; 171(2):261-70.
    View in: PubMed
  75. Lozoff B, Beard J, Connor J, Barbara F, Georgieff M, Schallert T. Long-lasting neural and behavioral effects of iron deficiency in infancy. Nutr Rev. 2006 May; 64(5 Pt 2):S34-43; discussion S72-91.
    View in: PubMed
  76. Beard JL, Felt B, Schallert T, Burhans M, Connor JR, Georgieff MK. Moderate iron deficiency in infancy: biology and behavior in young rats. Behav Brain Res. 2006 Jun 30; 170(2):224-32.
    View in: PubMed
  77. Clardy SL, Earley CJ, Allen RP, Beard JL, Connor JR. Ferritin subunits in CSF are decreased in restless legs syndrome. J Lab Clin Med. 2006 Feb; 147(2):67-73.
    View in: PubMed
  78. Zinnanti WJ, Lazovic J, Wolpert EB, Antonetti DA, Smith MB, Connor JR, Woontner M, Goodman SI, Cheng KC. A diet-induced mouse model for glutaric aciduria type I. Brain. 2006 Apr; 129(Pt 4):899-910.
    View in: PubMed
  79. Huang E, Ong WY, Go ML, Connor JR. Upregulation of iron regulatory proteins and divalent metal transporter-1 isoforms in the rat hippocampus after kainate induced neuronal injury. Exp Brain Res. 2006 Apr; 170(3):376-86.
    View in: PubMed
  80. Zhang X, Haaf M, Todorich B, Grosstephan E, Schieremberg H, Surguladze N, Connor JR. Cytokine toxicity to oligodendrocyte precursors is mediated by iron. Glia. 2005 Nov 15; 52(3):199-208.
    View in: PubMed
  81. Siddiq A, Ayoub IA, Chavez JC, Aminova L, Shah S, LaManna JC, Patton SM, Connor JR, Cherny RA, Volitakis I, Bush AI, Langsetmo I, Seeley T, Gunzler V, Ratan RR. Hypoxia-inducible factor prolyl 4-hydroxylase inhibition. A target for neuroprotection in the central nervous system. J Biol Chem. 2005 Dec 16; 280(50):41732-43.
    View in: PubMed
  82. Patton SM, Piñero DJ, Surguladze N, Beard J, Connor JR. Subcellular localization of iron regulatory proteins to Golgi and ER membranes. J Cell Sci. 2005 Oct 1; 118(Pt 19):4365-73.
    View in: PubMed
  83. Earley CJ, Connor JR, Beard JL, Clardy SL, Allen RP. Ferritin levels in the cerebrospinal fluid and restless legs syndrome: effects of different clinical phenotypes. Sleep. 2005 Sep; 28(9):1069-75.
    View in: PubMed
  84. Surguladze N, Patton S, Cozzi A, Fried MG, Connor JR. Characterization of nuclear ferritin and mechanism of translocation. Biochem J. 2005 Jun 15; 388(Pt 3):731-40.
    View in: PubMed
  85. Lee SY, Connor JR. Regulation of Hfe by stress factors in BV-2 cells. Neurobiol Aging. 2005 Jun; 26(6):803-12.
    View in: PubMed
  86. McEchron MD, Cheng AY, Liu H, Connor JR, Gilmartin MR. Perinatal nutritional iron deficiency permanently impairs hippocampus-dependent trace fear conditioning in rats. Nutr Neurosci. 2005 Jun; 8(3):195-206.
    View in: PubMed
  87. Beard JL, Wiesinger JA, Li N, Connor JR. Brain iron uptake in hypotransferrinemic mice: influence of systemic iron status. J Neurosci Res. 2005 Jan 1-15; 79(1-2):254-61.
    View in: PubMed
  88. Wang XS, Lee S, Simmons Z, Boyer P, Scott K, Liu W, Connor J. Increased incidence of the Hfe mutation in amyotrophic lateral sclerosis and related cellular consequences. J Neurol Sci. 2004 Dec 15; 227(1):27-33.
    View in: PubMed
  89. Henderson RJ, Patton SM, Connor JR. Development of a fluorescent reporter to assess iron regulatory protein activity in living cells. Biochim Biophys Acta. 2005 Mar 22; 1743(1-2):162-8.
    View in: PubMed
  90. Zecca L, Youdim MB, Riederer P, Connor JR, Crichton RR. Iron, brain ageing and neurodegenerative disorders. Nat Rev Neurosci. 2004 Nov; 5(11):863-73.
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  91. Knutson M, Menzies S, Connor J, Wessling-Resnick M. Developmental, regional, and cellular expression of SFT/UbcH5A and DMT1 mRNA in brain. J Neurosci Res. 2004 Jun 1; 76(5):633-41.
    View in: PubMed
  92. Wang X, Wiesinger J, Beard J, Felt B, Menzies S, Earley C, Allen R, Connor J. Thy1 expression in the brain is affected by iron and is decreased in Restless Legs Syndrome. J Neurol Sci. 2004 May 15; 220(1-2):59-66.
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  93. Connor JR, Wang XS, Patton SM, Menzies SL, Troncoso JC, Earley CJ, Allen RP. Decreased transferrin receptor expression by neuromelanin cells in restless legs syndrome. Neurology. 2004 May 11; 62(9):1563-7.
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  94. Todorich BM, Connor JR. Redox metals in Alzheimer's disease. Ann N Y Acad Sci. 2004 Mar; 1012:171-8.
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  95. Surguladze N, Thompson KM, Beard JL, Connor JR, Fried MG. Interactions and reactions of ferritin with DNA. J Biol Chem. 2004 Apr 9; 279(15):14694-702.
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  96. Burdo JR, Simpson IA, Menzies S, Beard J, Connor JR. Regulation of the profile of iron-management proteins in brain microvasculature. J Cereb Blood Flow Metab. 2004 Jan; 24(1):67-74.
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  97. Connor JR. Myelin breakdown in Alzheimer's disease: a commentary. Neurobiol Aging. 2004 Jan; 25(1):45-7.
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  98. Beard JL, Wiesinger JA, Connor JR. Pre- and postweaning iron deficiency alters myelination in Sprague-Dawley rats. Dev Neurosci. 2003 Sep-Oct; 25(5):308-15.
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  99. Connor JR, Boyer PJ, Menzies SL, Dellinger B, Allen RP, Ondo WG, Earley CJ. Neuropathological examination suggests impaired brain iron acquisition in restless legs syndrome. Neurology. 2003 Aug 12; 61(3):304-9.
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  100. Saleh MC, Espinosa de los Monteros A, de Arriba Zerpa GA, Fontaine I, Piaud O, Djordjijevic D, Baroukh N, Garcia Otin AL, Ortiz E, Lewis S, Fiette L, Santambrogio P, Belzung C, Connor JR, de Vellis J, Pasquini JM, Zakin MM, Baron B, Guillou F. Myelination and motor coordination are increased in transferrin transgenic mice. J Neurosci Res. 2003 Jun 1; 72(5):587-94.
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  101. Beard JL, Connor JR. Iron status and neural functioning. Annu Rev Nutr. 2003; 23:41-58.
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  102. Connor JR. Iron transport proteins in the diseased brain. J Neurol Sci. 2003 Mar 15; 207(1-2):112-3.
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  103. Siddappa AJ, Rao RB, Wobken JD, Casperson K, Leibold EA, Connor JR, Georgieff MK. Iron deficiency alters iron regulatory protein and iron transport protein expression in the perinatal rat brain. Pediatr Res. 2003 May; 53(5):800-7.
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  104. Burdo JR, Connor JR. Brain iron uptake and homeostatic mechanisms: an overview. Biometals. 2003 Mar; 16(1):63-75.
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  105. Han J, Day JR, Connor JR, Beard JL. Gene expression of transferrin and transferrin receptor in brains of control vs. iron-deficient rats. Nutr Neurosci. 2003 Feb; 6(1):1-10.
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  106. Thompson K, Menzies S, Muckenthaler M, Torti FM, Wood T, Torti SV, Hentze MW, Beard J, Connor J. Mouse brains deficient in H-ferritin have normal iron concentration but a protein profile of iron deficiency and increased evidence of oxidative stress. J Neurosci Res. 2003 Jan 1; 71(1):46-63.
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  107. Han J, Day JR, Connor JR, Beard JL. H and L ferritin subunit mRNA expression differs in brains of control and iron-deficient rats. J Nutr. 2002 Sep; 132(9):2769-74.
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  108. Wang XS, Ong WY, Connor JR. A light and electron microscopic study of divalent metal transporter-1 distribution in the rat hippocampus, after kainate-induced neuronal injury. Exp Neurol. 2002 Sep; 177(1):193-201.
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  109. Zywicke HA, van Gelderen P, Connor JR, Burdo JR, Garrick MD, Dolan KG, Frank JA, Bulte JW. Microscopic R2* mapping of reduced brain iron in the Belgrade rat. Ann Neurol. 2002 Jul; 52(1):102-5.
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  110. Siddappa AJ, Rao RB, Wobken JD, Leibold EA, Connor JR, Georgieff MK. Developmental changes in the expression of iron regulatory proteins and iron transport proteins in the perinatal rat brain. J Neurosci Res. 2002 Jun 15; 68(6):761-75.
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  111. Thompson KJ, Fried MG, Ye Z, Boyer P, Connor JR. Regulation, mechanisms and proposed function of ferritin translocation to cell nuclei. J Cell Sci. 2002 May 15; 115(Pt 10):2165-77.
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  112. Robb SJ, Connor JR. Nitric oxide protects astrocytes from oxidative stress. Ann N Y Acad Sci. 2002 May; 962:93-102.
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  113. Malecki EA, Cable EE, Isom HC, Connor JR. The lipophilic iron compound TMH-ferrocene [(3,5,5-trimethylhexanoyl)ferrocene] increases iron concentrations, neuronal L-ferritin, and heme oxygenase in brains of BALB/c mice. Biol Trace Elem Res. 2002 Apr; 86(1):73-84.
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  114. Takeda A, Takatsuka K, Connor JR, Oku N. Abnormal iron delivery to the bone marrow in neonatal hypotransferrinemic mice. Biometals. 2002 Mar; 15(1):33-6.
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  115. Hulet SW, Menzies S, Connor JR. Ferritin binding in the developing mouse brain follows a pattern similar to myelination and is unaffected by the jimpy mutation. Dev Neurosci. 2002; 24(2-3):208-13.
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  116. Piñero DJ, Li N, Hu J, Beard JL, Connor JR. The intracellular location of iron regulatory proteins is altered as a function of iron status in cell cultures and rat brain. J Nutr. 2001 Nov; 131(11):2831-6.
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  117. Connor JR, Menzies SL, Burdo JR, Boyer PJ. Iron and iron management proteins in neurobiology. Pediatr Neurol. 2001 Aug; 25(2):118-29.
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  118. Cheepsunthorn P, Radov L, Menzies S, Reid J, Connor JR. Characterization of a novel brain-derived microglial cell line isolated from neonatal rat brain. Glia. 2001 Jul; 35(1):53-62.
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  119. Thompson KJ, Shoham S, Connor JR. Iron and neurodegenerative disorders. Brain Res Bull. 2001 May 15; 55(2):155-64.
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  120. Cheepsunthorn P, Palmer C, Menzies S, Roberts RL, Connor JR. Hypoxic/ischemic insult alters ferritin expression and myelination in neonatal rat brains. J Comp Neurol. 2001 Mar 19; 431(4):382-96.
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  121. Piñero DJ, Hu J, Cook BM, Scaduto RC, Connor JR. Interleukin-1beta increases binding of the iron regulatory protein and the synthesis of ferritin by increasing the labile iron pool. Biochim Biophys Acta. 2000 Sep 20; 1497(3):279-88.
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  122. Ye Z, Connor JR. cDNA cloning by amplification of circularized first strand cDNAs reveals non-IRE-regulated iron-responsive mRNAs. Biochem Biophys Res Commun. 2000 Aug 18; 275(1):223-7.
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  123. Hulet SW, Heyliger SO, Powers S, Connor JR. Oligodendrocyte progenitor cells internalize ferritin via clathrin-dependent receptor mediated endocytosis. J Neurosci Res. 2000 Jul 1; 61(1):52-60.
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  124. Piñero DJ, Hu J, Connor JR. Alterations in the interaction between iron regulatory proteins and their iron responsive element in normal and Alzheimer's diseased brains. Cell Mol Biol (Noisy-le-grand). 2000 Jun; 46(4):761-76.
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  125. Han J, Day JR, Thomson K, Connor JR, Beard JL. Iron deficiency alters H- and L-ferritin expression in rat brain. Cell Mol Biol (Noisy-le-grand). 2000 May; 46(3):517-28.
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  126. Ye Z, Connor JR. Identification of iron responsive genes by screening cDNA libraries from suppression subtractive hybridization with antisense probes from three iron conditions. Nucleic Acids Res. 2000 Apr 15; 28(8):1802-7.
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  127. Malecki EA, Buhl KM, Beard JL, Jacobs CR, Connor JR, Donahue HJ. Bone structural and mechanical properties are affected by hypotransferrinemia but not by iron deficiency in mice. J Bone Miner Res. 2000 Feb; 15(2):271-7.
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  128. Piñero DJ, Li NQ, Connor JR, Beard JL. Variations in dietary iron alter brain iron metabolism in developing rats. J Nutr. 2000 Feb; 130(2):254-63.
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  129. Malecki EA, Cook BM, Devenyi AG, Beard JL, Connor JR. Transferrin is required for normal distribution of 59Fe and 54Mn in mouse brain. J Neurol Sci. 1999 Nov 30; 170(2):112-8.
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  130. Ye Z, Connor JR. Screening of transcriptionally regulated genes following iron chelation in human astrocytoma cells. Biochem Biophys Res Commun. 1999 Nov 2; 264(3):709-13.
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  131. Debinski W, Gibo DM, Hulet SW, Connor JR, Gillespie GY. Receptor for interleukin 13 is a marker and therapeutic target for human high-grade gliomas. Clin Cancer Res. 1999 May; 5(5):985-90.
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  132. Hulet SW, Powers S, Connor JR. Distribution of transferrin and ferritin binding in normal and multiple sclerotic human brains. J Neurol Sci. 1999 May 1; 165(1):48-55.
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  133. Robb SJ, Gaspers LD, Wright KJ, Thomas AP, Connor JR. Influence of nitric oxide on cellular and mitochondrial integrity in oxidatively stressed astrocytes. J Neurosci Res. 1999 Apr 15; 56(2):166-76.
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  134. Malecki EA, Devenyi AG, Beard JL, Connor JR. Existing and emerging mechanisms for transport of iron and manganese to the brain. J Neurosci Res. 1999 Apr 15; 56(2):113-22.
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  135. Palmer C, Menzies SL, Roberts RL, Pavlick G, Connor JR. Changes in iron histochemistry after hypoxic-ischemic brain injury in the neonatal rat. J Neurosci Res. 1999 Apr 1; 56(1):60-71.
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  136. Robb SJ, Robb-Gaspers LD, Scaduto RC, Thomas AP, Connor JR. Influence of calcium and iron on cell death and mitochondrial function in oxidatively stressed astrocytes. J Neurosci Res. 1999 Mar 15; 55(6):674-86.
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  137. Hulet SW, Hess EJ, Debinski W, Arosio P, Bruce K, Powers S, Connor JR. Characterization and distribution of ferritin binding sites in the adult mouse brain. J Neurochem. 1999 Feb; 72(2):868-74.
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  138. Vannucci RC, Connor JR, Mauger DT, Palmer C, Smith MB, Towfighi J, Vannucci SJ. Rat model of perinatal hypoxic-ischemic brain damage. J Neurosci Res. 1999 Jan 15; 55(2):158-63.
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  139. Burdo JR, Martin J, Menzies SL, Dolan KG, Romano MA, Fletcher RJ, Garrick MD, Garrick LM, Connor JR. Cellular distribution of iron in the brain of the Belgrade rat. Neuroscience. 1999; 93(3):1189-96.
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  140. Cheepsunthorn P, Palmer C, Connor JR. Cellular distribution of ferritin subunits in postnatal rat brain. J Comp Neurol. 1998 Oct 12; 400(1):73-86.
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  141. Malecki EA, Devenyi AG, Beard JL, Connor JR. Transferrin response in normal and iron-deficient mice heterozygotic for hypotransferrinemia; effects on iron and manganese accumulation. Biometals. 1998 Sep; 11(3):265-76.
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  142. Robb SJ, Connor JR. An in vitro model for analysis of oxidative death in primary mouse astrocytes. Brain Res. 1998 Mar 30; 788(1-2):125-32.
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  143. Cable EE, Connor JR, Isom HC. Accumulation of iron by primary rat hepatocytes in long-term culture: changes in nuclear shape mediated by non-transferrin-bound forms of iron. Am J Pathol. 1998 Mar; 152(3):781-92.
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  144. Takeda A, Devenyi A, Connor JR. Evidence for non-transferrin-mediated uptake and release of iron and manganese in glial cell cultures from hypotransferrinemic mice. J Neurosci Res. 1998 Feb 15; 51(4):454-62.
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  145. Erikson KM, Pinero DJ, Connor JR, Beard JL. Regional brain iron, ferritin and transferrin concentrations during iron deficiency and iron repletion in developing rats. J Nutr. 1997 Oct; 127(10):2030-8.
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  146. Focht SJ, Snyder BS, Beard JL, Van Gelder W, Williams LR, Connor JR. Regional distribution of iron, transferrin, ferritin, and oxidatively-modified proteins in young and aged Fischer 344 rat brains. Neuroscience. 1997 Jul; 79(1):255-61.
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  147. Dickinson TK, Devenyi AG, Connor JR. Distribution of injected iron 59 and manganese 54 in hypotransferrinemic mice. J Lab Clin Med. 1996 Sep; 128(3):270-8.
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  148. Hu J, Connor JR. Demonstration and characterization of the iron regulatory protein in human brain. J Neurochem. 1996 Aug; 67(2):838-44.
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  149. Connor JR, Menzies SL. Relationship of iron to oligodendrocytes and myelination. Glia. 1996 Jun; 17(2):83-93.
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  150. Connor JR, Menzies SL. Cellular management of iron in the brain. J Neurol Sci. 1995 Dec; 134 Suppl:33-44.
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  151. Connor JR, Snyder BS, Arosio P, Loeffler DA, LeWitt P. A quantitative analysis of isoferritins in select regions of aged, parkinsonian, and Alzheimer's diseased brains. J Neurochem. 1995 Aug; 65(2):717-24.
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  152. Chen Q, Connor JR, Beard JL. Brain iron, transferrin and ferritin concentrations are altered in developing iron-deficient rats. J Nutr. 1995 Jun; 125(6):1529-35.
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  153. Connor JR, Pavlick G, Karli D, Menzies SL, Palmer C. A histochemical study of iron-positive cells in the developing rat brain. J Comp Neurol. 1995 Apr 24; 355(1):111-23.
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  154. Dickinson TK, Connor JR. Cellular distribution of iron, transferrin, and ferritin in the hypotransferrinemic (Hp) mouse brain. J Comp Neurol. 1995 Apr 24; 355(1):67-80.
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  155. Roskams AJ, Connor JR. Iron, transferrin, and ferritin in the rat brain during development and aging. J Neurochem. 1994 Aug; 63(2):709-16.
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  156. Connor JR, Boeshore KL, Benkovic SA, Menzies SL. Isoforms of ferritin have a specific cellular distribution in the brain. J Neurosci Res. 1994 Mar 1; 37(4):461-5.
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  157. Dickinson TK, Connor JR. Histological analysis of selected brain regions of hypotransferrinemic mice. Brain Res. 1994 Jan 28; 635(1-2):169-78.
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  158. Connor JR. Iron acquisition and expression of iron regulatory proteins in the developing brain: manipulation by ethanol exposure, iron deprivation and cellular dysfunction. Dev Neurosci. 1994; 16(5-6):233-47.
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  159. Connor JR. Iron regulation in the brain at the cell and molecular level. Adv Exp Med Biol. 1994; 356:229-38.
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  160. Benkovic SA, Connor JR. Ferritin, transferrin, and iron in selected regions of the adult and aged rat brain. J Comp Neurol. 1993 Dec 1; 338(1):97-113.
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  161. Connor JR, Roskams AJ, Menzies SL, Williams ME. Transferrin in the central nervous system of the shiverer mouse myelin mutant. J Neurosci Res. 1993 Dec 1; 36(5):501-7.
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  162. Connor JR, Tucker P, Johnson M, Snyder B. Ceruloplasmin levels in the human superior temporal gyrus in aging and Alzheimer's disease. Neurosci Lett. 1993 Sep 3; 159(1-2):88-90.
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  163. Roskams AJ, Connor JR. Transferrin receptor expression in myelin deficient (md) rats. J Neurosci Res. 1992 Mar; 31(3):421-7.
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  164. Connor JR, Snyder BS, Beard JL, Fine RE, Mufson EJ. Regional distribution of iron and iron-regulatory proteins in the brain in aging and Alzheimer's disease. J Neurosci Res. 1992 Feb; 31(2):327-35.
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  165. Connor JR, Benkovic SA. Iron regulation in the brain: histochemical, biochemical, and molecular considerations. Ann Neurol. 1992; 32 Suppl:S51-61.
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  166. Connor JR, Menzies SL, St Martin SM, Mufson EJ. A histochemical study of iron, transferrin, and ferritin in Alzheimer's diseased brains. J Neurosci Res. 1992 Jan; 31(1):75-83.
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  167. Bartlett WP, Li XS, Connor JR. Expression of transferrin mRNA in the CNS of normal and jimpy mice. J Neurochem. 1991 Jul; 57(1):318-22.
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  168. Roskams AJ, Connor JR. Aluminum access to the brain: a role for transferrin and its receptor. Proc Natl Acad Sci U S A. 1990 Nov; 87(22):9024-7.
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  169. Lin HH, Snyder BS, Connor JR. Transferrin expression in myelinated and non-myelinated peripheral nerves. Brain Res. 1990 Sep 3; 526(2):217-20.
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  170. Connor JR, Menzies SL. Altered cellular distribution of iron in the central nervous system of myelin deficient rats. Neuroscience. 1990; 34(1):265-71.
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  171. Lin HH, Connor JR. The development of the transferrin-transferrin receptor system in relation to astrocytes, MBP and galactocerebroside in normal and myelin-deficient rat optic nerves. Brain Res Dev Brain Res. 1989 Oct 1; 49(2):281-93.
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  172. Gerber MR, Connor JR. Do oligodendrocytes mediate iron regulation in the human brain? Ann Neurol. 1989 Jul; 26(1):95-8.
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  173. Diamond MC, Connor JR. Plasticity of the aging cerebral cortex. Exp Brain Res. 1982; Suppl 5:36-44.
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  174. Connor JR, Diamond MC, Johnson RE. Aging and environmental influences on two types of dendritic spines in the rat occipital cortex. Exp Neurol. 1980 Nov; 70(2):371-9.
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  175. Connor JR, Diamond MC, Johnson RE. Occipital cortical morphology of the rat: alterations with age and environment. Exp Neurol. 1980 Apr; 68(1):158-70.
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