Evidence for Iron Mismanagement in the Brain in Neurological Disorders

  • James R. Connor


Studies on manipulation of iron in the diet, both during development and in adults, have clearly established that iron is required for normal neurological function. A deficiency in iron availability to the brain may directly affect the general metabolic activity of the brain by decreasing the function of cytochrome oxidase, glucose 6-phosphate dehydrogenase, NADH dehydrogenase, succinic dehydrogenase, and aldehyde dehydrogenase—all of which require iron as an essential cofactor and are relatively elevated in brain (Cammer, 1984). Also, the brain is rich in myelin, and iron is required for the biosynthesis of cholesterol and lipids, which are key components of myelin and whose biosynthesis occurs in the brain at higher levels than in other organs (Larkin and Rao, 1990; Pleasure et al., 1984). Finally, specific neurotransmitter systems such as GABA, dopamine, and norepinephrine require iron for synthesis (see Chapter 1). The link between dopaminergic dysfunction and iron is particularly strong; indeed the substantia nigra (SN), the site of dopaminergic cell bodies in the brain, is an iron-rich area in the brain (Benkovic and Connor, 1993).


Substantia Nigra Iron Uptake Transferrin Receptor Iron Accumulation Neuritic Plaque 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Aldred, A., Dickson, P., Marley, P., and Schreiber, G., 1987, Distribution of transferrin synthesis in brain and other tissues, J. Biol. Chem. 262:5293–5297.PubMedGoogle Scholar
  2. Aoki, S., Okada, Y, Nishimura, K., Barkovich, A. J., Kjos, B. O., Brasch, R. C., and Norman, D., 1989, Normal deposition of brain iron in childhood and adolescence: MR imaging at 1.5 T, Radiology 172:381–385.PubMedGoogle Scholar
  3. Balla, G., Jacob, H. S., Balla, J., Rosenberg, M., Nath, K., Apple, F., Eaton, J. W., and Vercellotti, J. R., 1992, Ferritin: A cytoprotective antioxidant strategem of endothelium, J. Biol. Chem. 267:18148–18153.PubMedGoogle Scholar
  4. Bartlett, W. P., Li, X.-S., and Connor, J. R., 1991, Expression of transferrin mRNA in the CNS of normal and jimpy CNS, J. Neurochem. 57:318–322.PubMedCrossRefGoogle Scholar
  5. Baynes, R. D., and Bothwell, T. H., 1991, Iron deficiency, Ann. Rev. Nutr. 11:133–48.Google Scholar
  6. Beard, J. L., Connor, J. R., and Jones, B. C., 1993, Iron in the brain, Nutr. Rev. 51:157–170.PubMedCrossRefGoogle Scholar
  7. Benkovic, S., and Connor, J. R., 1993, Ferritin, transferrin and iron in normal and aged rat brains, J. Comp. Neurol. 338:97–113.PubMedCrossRefGoogle Scholar
  8. Bickel, U., Yoshikawa, T., Landaw, E. M., Faull, K. F., and Pardridge, W. M., 1993, Pharmacologic effect in vivo in brain by vector-mediated peptide drug delivery, Proc. Natl. Acad. Sci. USA 90:2618–2622.PubMedCrossRefGoogle Scholar
  9. Blissman, G., Menzies, S., Beard, J., Palmer, C., and Connor, J., 1996, The expression of ferritin subunits and iron in oligodendrocytes in neonatal porcine brains, Dev. Neurosci. (in press).Google Scholar
  10. Bloch, B., Popovici, T., Levin, M. J., Tuil, D., and Kahn, A., 1985, Transferrin gene expression visualized in oligodendrocytes of the rat brain by using in situ hybridization and immunohistochemistry, Proc. Natl. Acad. Sci. USA 81:6706–6710.CrossRefGoogle Scholar
  11. Bodovitz, S., Falduto, M. T., Frail, D. E., and Klein, W. L., 1995, Iron levels modulate α-secretase cleavage of amyloid precursor protein, J. Neurochem. 64:307–315.PubMedCrossRefGoogle Scholar
  12. Bowern, N., Ramshaw, I. A., Clark, I. A., and Doherty, P. C., 1984, Inhibition of autoimmune neuropathological process by treatment with an iron-chelating agent, J. Exp. Med. 160:1532–1543.PubMedCrossRefGoogle Scholar
  13. Broyles, R. H., Blair, F. C., Kyker, K. D., Kurien, B. T, Steward, D. R., Hala’sz, H., Berg, P. E., and Schechter, A. N., 1995, A ferritin-like protein binds to a highly conserved CAGTGC sequence in the β-globin promoter, in: Sickle Cell Disease and Thalassemias: New Trends in Therapy, Volume 234 (Y Beuzard, B. Lubin, and J. Ross, eds.), Colloque INSERM/John Libbey Eurotext Ldt., pp. 43–51.Google Scholar
  14. Cairo, G., and Pietrangelo, A., 1994, Transferrin receptor gene expression during rat liver regeneration, J. Biol. Chem. 269:6405–6409.PubMedGoogle Scholar
  15. Cammer, W., 1984, Oligodendrocyte associated enzymes, in: Oligodendroglia (W. T. Norton, ed.), Plenum Press, New York, pp. 199–232.Google Scholar
  16. Chen, Q., Connor, J. R., and Beard, J. L., 1995, Brain iron, transferrin and ferritin concentrations are altered in developing iron-deficient rats, J. Nutr. 125:1529–1535.PubMedGoogle Scholar
  17. Connor, J. R., 1993, Cellular and regional maintenance of iron homeostasis in the brain: normal and diseased states, in: Iron in Central Nervous System Disorders (P. Riederer and M. B. H. Youdim, eds.), Springer-Verlag, Wien, pp. 1–18.CrossRefGoogle Scholar
  18. Connor, J. R., 1994, Iron acquisition and expression of iron regulatory proteins in the developing brain: Manipulation by ethanol exposure, iron deprivation and cellular dysfunction, Dev. Neurosci. 16:233–247.PubMedCrossRefGoogle Scholar
  19. Connor, J. R., Boeshore, K. L., Benkovic, S. A., and Menzies, S. L., 1994, Isoforms of ferritin have a specific cellular distribution in the brain, J. Neurosci. Res. 37:461–465.PubMedCrossRefGoogle Scholar
  20. Connor, J. R., and Fine, R. E., 1987, Development of transferrin-positive oligodendrocytes in the rat central nervous system, J. Neurosci. Res. 17:51–59.PubMedCrossRefGoogle Scholar
  21. Connor, J. R., and Menzies, S. L., 1995, Cellular management of iron in the brain, J. Neurol. Sci. 134:33–44.PubMedCrossRefGoogle Scholar
  22. Connor, J. R., and Menzies, S. L., 1996, Relationship of iron to oligodendrocytes and myelination, Glia 17:83–93.PubMedCrossRefGoogle Scholar
  23. Connor, J. R., Phillips, T. M., Lakshman, M. R., Barron, K. D., Fine, R. E., and Csiza, C. K., 1987, Regional variation in the levels of transferrin in the CNS of normal and myelin-deficient rats, J. Neurochem. 49:1523–1529.PubMedCrossRefGoogle Scholar
  24. Connor, J. R., Menzies, S. L., St. Martin, S., and Mufson, E. J., 1990, The cellular distribution of transferrin, ferritin and iron in the human brain, J. Neurosci. Res. 27:595–611.PubMedCrossRefGoogle Scholar
  25. Connor, J. R., Menzies, S. L., St. Martin, S., Fine, R. E., and Mufson, E. J., 1992a, Altered cellular distribution of transferrin, ferritin and iron in Alzheimer’s diseased brains, J. Neurosci. Res. 31:75–85.PubMedCrossRefGoogle Scholar
  26. Connor, J. R., Snyder, B. S., Beard, J. L., Fine, R. E., and Mufson, E. J., 1992b, The regional distribution of iron and iron regulatory proteins in the brain in aging and Alzheimer’s disease, J. Neurosci. Res. 31:327–335.PubMedCrossRefGoogle Scholar
  27. Connor, J. R., Roskams, A. J. I., Menzies, S. L., and Williams, M. E., 1993, Transferrin in the central nervous system of the shiverer mouse myelin mutant, J. Neurosci. Res. 36:501–507.PubMedCrossRefGoogle Scholar
  28. Connor, J. R., Pavlick, G., Karli, D., Menzies, S. L., and Palmer, C., 1995a, A histochemical study of iron-positive cells in the developing rat brain, J. Comp. Neurol. 355:111–123.PubMedCrossRefGoogle Scholar
  29. Connor, J. R., Snyder, B. S., Arosio, P., Loeffler, D. A., and LeWitt, P., 1995b, A quantitative analysis of isoferritins in select regions of aged, Parkinsonian and Alzheimer’s diseased brains, J. Neurochem. 65:717–724.PubMedCrossRefGoogle Scholar
  30. Crowe, A., and Morgan, E. H., 1992, Iron and transferrin uptake by brain and cerebrospinal fluid in the rat, Brain Res. 592:8–16.PubMedCrossRefGoogle Scholar
  31. Dallman, P., and Spirito, R. A., 1977, Brain iron in the rat: Extremely slow turnover in normal rat may explain the long-lasting effects of early iron-deficiency, J. Nutr. 107:1075–1081.PubMedGoogle Scholar
  32. Dexter, D. T., Carayon, A., Vidailhet, M., Ruberg, M., Agid, F., Agid, Y, Lees, A. J., Wells, F. R., Jenner, P., and Marsden, C. D., 1990, Decreased ferritin levels in brain in Parkinson’s disease, J. Neurochem. 55:16–20.PubMedCrossRefGoogle Scholar
  33. Dickinson, T. K., and Connor, J. R., 1994, Histological analysis of selected brain regions of the hypotransferrinemic mouse, Brain Res. 635:169–178.PubMedCrossRefGoogle Scholar
  34. Dickinson, T. K., and Connor, J. R., 1995, Cellular distribution of iron, transferrin and ferritin in the hypotransferrinemic (Hp) mouse brain, J. Comp. Neurol. 355:67–80.PubMedCrossRefGoogle Scholar
  35. Dickinson, T. K., Devenyi, A. G., and Connor, J. R., 1996, Distribution of injected iron 59 and manganese 54 in hypotransferrinemic mice, J. Lab. Clin. Med. 128:270–278.PubMedCrossRefGoogle Scholar
  36. Drayer, B., Burger, P., Hurwita, B., Dawson, D., and Cain, J., 1987, Reduced signal intensity on MR images of thalamus and putamen in multiple sclerosis: Increased iron content? AJNR 8:413–419.Google Scholar
  37. Dwork, A. J., 1994, Effects of diet and development upon the uptake and distribution of cerebral iron, J. Neurol. Sci. 134(supplement):45–51.CrossRefGoogle Scholar
  38. Dwork, A. J., Schon, E. A., and Herbert, J., 1988, Nonidentical distribution of transferrin and iron in human brain, Neuroscience 27:333–335.PubMedCrossRefGoogle Scholar
  39. Dwork, A. J., Lawler, G., Zybert, P. A., Durkin, M., Osman, M., Wilson, N., and Barkai, A. I., 1990, An autoradiographic study of the uptake and distribution of iron by the brain of the you rat, Brain Res. 518:31–39.PubMedCrossRefGoogle Scholar
  40. Dziegielewska, K. M., Evans, C. A. N., Malinowskq, D. H., Mollgârd, K., Reynolds, M. L., and Saunders, N. R., 1980, Blood-cerebrospinal fluid transfer of plasma proteins during fetal development in the sheep, J. Physiol 300:457–465.PubMedGoogle Scholar
  41. Earle, K. M., 1968, Studies in Parkinson’s disease including x-ray fluorescent spectroscopy of formalin fixed brain tissue, J. Neuropathol Exp. Neurol 27:1–14.PubMedCrossRefGoogle Scholar
  42. Ehmann, W. D., Markesbery, W. R., Alauddin, M., Hossain, T., and Brubaker, E. H., 1986, Brain trace elements in Alzheimer’s disease, Neurotoxicology 7:197.Google Scholar
  43. Elovaara, I., Icen, A., Palo, J., and Erkinjuntti, T., 1985, CSF in Alzheimer’s disease, J. Neurol Sci. 70:73–80.PubMedCrossRefGoogle Scholar
  44. Espinosa de los Monteras, A., Kumar, S., and Scully, S., 1990, Transferrin gene expression and secretion by rat brain cells in vitro, J. Neurosci. Res. 18:299–304.Google Scholar
  45. Faucheux, B. A., Hirsch, E. C., Villares, J., Selimi, F., Mouatt-Prigent, A., Javoy-Agid, F., and Agid, Y., 1993, Distribution of 125-I ferrotransferrin binding sites in the mesencephalon of control subjects and patients with Parkinson’s disease, J. Neurochem. 60:2338–234.PubMedCrossRefGoogle Scholar
  46. Faucheux, B. A., Nillesse, N., Damier, P., Spik, G., Mouatt-Prigent, A., Pierce, A., Leveugle, B., Kubis, N., Hauw, J-J., and Agid, Y, 1995, Expression of lactoferrin receptors is increased in the mesencephalon of patients with Parkinson’s disease, Proc. Natl. Acad. Sci. USA 92:9603–9607.PubMedCrossRefGoogle Scholar
  47. Fisher, M., Levine, P. H., Weiner, B. H., Vaudreuil, C. H., Natale, A., Johnson, M. H., and Hoogasian, J. J., 1988, Monocyte and polymorphonuclear leukocyte toxic oxygen metabolite production in multiple sclerosis, Inflammation 12:123–131.PubMedCrossRefGoogle Scholar
  48. Fishman, J. B., Rubin, J. B., Handrahan, J. V., Connor, J. R., and Fine, R. E., 1987, Receptor mediated uptake of transferrin across the blood brain barrier, J. Neurosci. Res. 18:299–305.PubMedCrossRefGoogle Scholar
  49. Friden, P. M., Walus, L. R., Watson, P., Doctrow, S. R., Kozarich, J. W., Backman, C., Bergman, H., Hoffer, B., Bloom, F., and Granholm, A.-C, 1993, Blood-brain-barrier penetration and in vivo activity of an NGF conjugate, Science 259:373–377.PubMedCrossRefGoogle Scholar
  50. Giometto, B., Bozza, F., Argentiero, V., Gallo, P., Pagni, S., Piccinno, M. G., and Tavolato, B., 1990, Transferrin receptor in rat central nervous system: An immunohistochemical study, J. Neurol Sci. 98:81.PubMedCrossRefGoogle Scholar
  51. Gocht, A., Keith, A. B., Candy, J. M., and Morris, C. M., 1993, Iron uptake in the brain of the myelin deficient rat, Neurosci. Lett. 154:187–190.PubMedCrossRefGoogle Scholar
  52. Good, P. F., Olanow, C. W., and Perl, D. P., 1992, Neuromelanin-containing neurons of the substantia nigra accumulate iron and aluminum in Parkinson’s disease: A LAMMA study, Brain Res. 593:343–346.PubMedCrossRefGoogle Scholar
  53. Goodman, L., 1953, Alzheimer’s disease: a clinicopathologic analysis of twenty-three cases with a theory of pathogenesis, J. Nerv. Ment. Dis. 118:97–130.PubMedCrossRefGoogle Scholar
  54. Graeber, M. B., Raivich, G., and Kreutzberg, G. W., 1989, Increase in transferrin receptors and iron uptake in regenerating motor neurons, J. Neurosci. Res. 23:342.PubMedCrossRefGoogle Scholar
  55. Griot, C., Vandevelde, M., Richard, A., Peterhasn, E., and Stocker, R., 1990, Selective degeneration of oligodendrocytes mediated by reactive oxygen species, Free Rad. Res. Comms. 11:181–193.CrossRefGoogle Scholar
  56. Grundke-Iqbal, I., Fleming, J., Tung, Y.-C, Lassman, H., Iqbal, K., and Joshi, J. G., 1990, Ferritin is a component of the neuritic plaque in Alzheimer’s dementia, Acta Neuropathol. 81:105–110.PubMedCrossRefGoogle Scholar
  57. Guo, B., Brown, F. M., Phillips, J. D., Yu, Y, and Leibold, E. A., 1995, Characterization and expression of iron regulatory protein 2 (IRP2), J. Biol Chem. 270:16259–16535.Google Scholar
  58. Guo, B., Yu, Y, and Leibold, E. A., 1994, Iron regulates cytoplasmic levels of a novel iron-responsive element-binding protein without aconitase activity, J. Biol. Chem. 269:24252–24260.PubMedGoogle Scholar
  59. Hallgren, B., and Sourander, P., 1958, The effect of age on the nonhaemin iron in the human brain, J. Neurochem. 3:41–51.PubMedCrossRefGoogle Scholar
  60. Hartung, H. P., Schafer, B., Heininger, K., and Toyka, K. V., 1988, Suppression of experimental autoimmune neuritis by the oxygen radical scavengers superoxide dismutase and catalase, Ann. Neurol. 23:453–460.PubMedCrossRefGoogle Scholar
  61. Henderson, B. R., Seiser, C., and Kuhn, L. C., 1993, Characterization of a second RNA-binding protein in rodents with specificity for iron-responsive elements, J. Biol Chem. 268:27327–27334.PubMedGoogle Scholar
  62. Hill, J. M., and Swizter, R. C., 1984, The regional distribution and cellular localization of iron in the rat brain, Neuroscience 11:595–603.PubMedCrossRefGoogle Scholar
  63. Hill, J. M., Ruff, M. R., Weber, R. J., and Pert, C. B., 1985, Transferrin receptors in rat brain: neuropeptide-like pattern and relationship to iron distribution, Proc. Natl. Acad. Sci. USA 82:4553.PubMedCrossRefGoogle Scholar
  64. Hu, J., and Connor, J. R., 1996, Characterization of the iron regulatory protein in the human brain, J. Neurochem. 67:838–844.PubMedCrossRefGoogle Scholar
  65. Hulet, S. W., Arosio, P., Debinski, W., Powers, S., and Connor, J. R., 1996, Demonstration and characterization of a ferritin receptor in the brain, FASEB J. 10(3):A251.Google Scholar
  66. Hunter, M. I. S., Nlemadim, B. C., and Davidson, D. L. W., 1985, Lipid peroxidation production and antioxidant proteins in plasma and cerebrospinal fluid from multiple sclerosis patients, Neurochem. Res. 10:1645–1652.PubMedCrossRefGoogle Scholar
  67. Jaffrey, S. R., Cohen, N. A., Rouault, T. A., Klausner, R. D., and Snyder, S. H., 1994, The iron responsive element binding protein: a target for synaptic actions of nitric oxide, Proc. Natl. Acad. Sci. USA 91:12994–12998.PubMedCrossRefGoogle Scholar
  68. Jefferies, W. A., Brandon, M. R., Hunt, S. V., Williams, A. F., Gatter, K. C., and Mason, D. Y, 1984, Transferrin receptor on endothelium of brain capillaries, Nature 312:162–163.PubMedCrossRefGoogle Scholar
  69. Johnson, D., Toms, R., and Weiner, H., 1989, Studies of myelin breakdown in vitro, in: Myelination and Demyelination (S. U. Kim, ed.), Plenum Press, New York, pp. 219–236.CrossRefGoogle Scholar
  70. Kalaria, R. N., Sromek, S. M., Grahovac, I., and Harik, S. I., 1992, Transferrin receptors of rat and human brain and cerebral microvessels and their status in Alzheimer’s disease, Brain Res. 585:87–93.PubMedCrossRefGoogle Scholar
  71. Kaneko, Y, Kitamoto, T., Tateosjo, J., and Yamaguchi, K., 1989, Ferritin immunohistochemistry as a marker for microglia, Acta Neuropathol. 79:129–136.PubMedCrossRefGoogle Scholar
  72. Kaur, C., and Ling, E. A., 1995, Transient expression of transferrin receptors and localization of iron in amoeboid microglia in postnatal rats, J. Anat. 186:165–173.PubMedGoogle Scholar
  73. Kim, Y S., and Kim, S. U., 1991, Oligodendroglial cell death induced by oxygen radicals and its protection by catalase, J. Neurosci. Res. 29:100–106.PubMedCrossRefGoogle Scholar
  74. Klausner, R. D., Rouault, T. A., and Harford, J. B., 1993, Regulating the fate of mRNA: The control of cellular iron metabolism, Cell 72:19–28.PubMedCrossRefGoogle Scholar
  75. Koeppen, A., 1995, The history of iron in the brain, J. Neurol. Sci. 134(supplement): 1–9.PubMedCrossRefGoogle Scholar
  76. Koeppen, A. H., and Borke, R. C., 1991, Experimental superficial siderosis of the central nervous system. I. Morphological observations, J. Neuropathol. Exp. Neurol. 50:579–594.PubMedCrossRefGoogle Scholar
  77. Larkin, E. C., and Rao, G. A., 1990, Importance of fetal and neonatal iron: Adequacy for normal development of central nervous system, in: Brain, Behaviour and Iron in the Infant Diet (J. Dobbing, ed.), Springer-Verlag, London, pp. 43–63.Google Scholar
  78. Levi, S., Yewdall, S. J., Harrison, P. M., Santambrogio, P., Cozzi, A., Rovida, E., Albertini, A., and Arosio, P., 1992, Evidence that H-L-chains have cooperative role in the iron uptake mechanism of human ferritin, Biochem. J. 288:591–596.PubMedGoogle Scholar
  79. Levine, M., Tuil, D., and Uzan, G., 1984, Expression of the transferrin gene during development of non-hepatic tissue, Biochem. Biophys. Res. Comm. 122:212.CrossRefGoogle Scholar
  80. Levine, S. M., 1991, Oligodendrocytes and myelin sheaths in normal, quaking and shiverer brains are enriched in iron, J. Neurosci. Res. 29:413–419.PubMedCrossRefGoogle Scholar
  81. Levine, S. M., 1992, The role of reactive oxygen species in the pathogenesis of multiple sclerosis, Med. Hypoth. 39:271–274.CrossRefGoogle Scholar
  82. Lin, H. H., and Connor, J. R., 1989, The development of the transferrin-transferrin receptor system in relation to astrocytes, MBP, and galactocerebroside in normal and myelin deficient rat optic nerves, Dev. Brain Res. 49:281–293.CrossRefGoogle Scholar
  83. Loeffler, D. A., Connor, J. R., Juneau, P. L., Snyder, B. S., Kanaley, L., DeMaggio, A. J., Nguyen, H., Brickman, M., and Le Witt, P. A., 1995, Transferrin and iron in normal, Alzheimer’s disease and Parkinson’s disease brain regions, J. Neurochem. 65:710–716.PubMedCrossRefGoogle Scholar
  84. Manges, K., and Connor, J. R., 1996, Heavy chain ferritin binds DNA, Soc. Neurosci. Abstr. 22(1):529.Google Scholar
  85. Mantyh, P. W, Ghilardi, J. R., Rogers, S., DeMaster, E., Allen, C. J., Stimson, E. R., and Maggio, J. E., 1993, Aluminum, iron and zinc ions promote aggregation of physiological concentrations of beta-amyloid peptide, J. Neurochem. 61:1171–1174.PubMedCrossRefGoogle Scholar
  86. Mash, D. C., Pablo, J., Flynn, D. D., Efange, S. M. N., and Weiner, W. J., 1990, Characterization and distribution of transferrin receptors in the rat brain, J. Neurochem. 55:1972–1978.PubMedCrossRefGoogle Scholar
  87. Mash, D. C., Pablo, J., Buck, B. E., Sanchez-Ramos, J., and Weiner, W. J., 1991, Distribution and number of transferrin receptors in Parkinson’s disease and in MPTP-treated mice, Exp. Neurol. 114:73–81.PubMedCrossRefGoogle Scholar
  88. Mitrovic, B., Ignarro, L. J., Montestruque, S., Smoll, A., and Merrill, J. E., 1994, Nitric oxide as a potential pathological mechanism in demyelination: Its differential effects on primary glial cells in vitro, Neuroscience 61:575–585.PubMedCrossRefGoogle Scholar
  89. Mitrovic, B., Ignarro, L. J., Vinters, H. V., Akers, M. A., Schmid, I., Uittenbogaart, C., and Merrill, J. E., 1995, Nitric oxide induces necrotic but not apoptotic death in oligodendrocytes, Neuroscience 65:531–539.PubMedCrossRefGoogle Scholar
  90. Moos, T., 1995a, Increased accumulation of transferrin by motor neurons of the mouse mutant progressive motor neuronopathy (pmn/pmn), J. Neurocytol 24:389–398.PubMedCrossRefGoogle Scholar
  91. Moos, T., 1995b, Age-dependent uptake and retrograde axonal transport of endogenous albumin and transferrin in rat motor neurons, Brain Res. 672:14–23.PubMedCrossRefGoogle Scholar
  92. Morris, C. M., Candy, J. M., Bloxham, C. A., and Edwardson, J. A., 1992a, Distribution of transferrin receptors in relation to cytochrome oxidase activity in the human spinal cord, lower brain stem and cerebellum, J. Neurol. Sci. 111:158–172.PubMedCrossRefGoogle Scholar
  93. Morris, C. M., Candy, J. M., Oakley, A. E., Bloxham, C. A., and Edwardson, J. A., 1992b, Histochemical distribution of non-haem iron in the human brain, Acta Anatom. 144:235–257.CrossRefGoogle Scholar
  94. Morris, C. M., Keith, A. B., Edwardson, J. A., and Pullen, R. G. L., 1992c, Uptake and distribution of iron and transferrin in the adult rat brain, J. Neurochem. 59:300–306.PubMedCrossRefGoogle Scholar
  95. New, H., Dziegielewska, K. M., and Saunders, N. R., 1983, Transferrin in fetal rat brain and cerebrospinal fluid, Int. J. Devl. Neurosci. 1:369–373.CrossRefGoogle Scholar
  96. Oka, A., Beliveau, M. J., Rosenberg, R A., and Volpe, J. J., 1993, Vulnerability of oligodenroglia to glutamate: Pharmacology, mechanisms and prevention, J. Neurosci. 13:1441–1453.PubMedGoogle Scholar
  97. Oloyede, O. B., Folayan, A. T., and Odutauga, A. A., 1992, Effects of low-iron status and deficiency of essential fatty acids on some biochemical constituents of rat brain, Biochem. Internat. 27:913–922.Google Scholar
  98. Pleasure, D., Kim, S. U., and Silberberg, D. H., 1984, In vitro studies of oligodendroglial lipid metabolism, in: Oligodendroglia (W. H. Norton, ed.), Plenum Press, New York, pp. 175–197.Google Scholar
  99. Pollitt, E., and Ponpon, I., 1993, Reversal of developmental delays in iron-deficient anaemic infants treated with iron, Lancet 341:1–4.PubMedCrossRefGoogle Scholar
  100. Powell, L. W., Alpert, E., Isselbacher, K. J., and Drysdale, J. W., 1974, Abnormality in tissue isoferritin distribution in idiopathic haemochromatosis, Nature 250:333–335.PubMedCrossRefGoogle Scholar
  101. Qi, Y., and Dawson, G., 1994, Hypoxia specifically and reversibly induces the synthesis of ferritin in oligodendrocytes and human oligodendrogliomas, J. Neurochem. 63:1485–1490.PubMedCrossRefGoogle Scholar
  102. Raivich, G., Graeber, M. B., Gehrmann, J., and Kreutzberg, G. W., 1991, Transferrin receptor expression and iron uptake in the injured and regenerating rat sciatic nerve, Eur. J. Neurosci. 3:919–927.PubMedCrossRefGoogle Scholar
  103. Reiderer, P., Sofie, E., Rausch, W.-D., Schmidt, B., Reynolds, G. P., Jellinger, K., and Joudim, M. B. H., 1989, Transition metals, ferritin, glutathione, and ascorbic acid in Parkinsonian brains, J. Neurochem. 52:515–520.CrossRefGoogle Scholar
  104. Reif, D. W., and Simmons, R. D., 1990, Nitric oxide mediates iron release from ferritin, Arch. Biochem. Biophys. 283:537–541.PubMedCrossRefGoogle Scholar
  105. Robinson, S. R., Noone, D. F., Kril, J., and Halliday, G. M., 1995, Most amyloid plaques contain ferritin-rich cells, Alzheimer’s Res. 1:191–196.Google Scholar
  106. Roskams, A. J. I., and Connor, J. R., 1992, The transferrin receptor in the myelin deficient (md) rat, J. Neurosci. Res. 31:421–427.PubMedCrossRefGoogle Scholar
  107. Roskams, A. J., and Connor, J. R., 1994, Iron, transferrin and ferritin in the rat brain during development and aging, J. Neurochem. 63:709–716.PubMedCrossRefGoogle Scholar
  108. Samaniego, F., Chin, J., Iwai, K., Rouault, T. A., and Klausner, R. D., 1994, Molecular characterization of a second iron-responsive element binding protein, iron regulatory protein 2. Structure, function, and post-translational regulation, J. Biol. Chem. 269:30904–30910.PubMedGoogle Scholar
  109. Sanyal, B., and Szuchet, S., 1995, Tumor necrosis factor a induces the transcription of the H chain ferritin gene in cultured oligodendrocytes, Soc. Neurosci. Abstr. 21:(part 1):3.Google Scholar
  110. Simpson, R. J., Raja, K. B., Halliwell, B., Evans, P. J., Aruoma, O. I., and Konjin, A. M., 1991, Iron speciation in hypotransferrinemic mouse serum, Biochem. Soc. Trans. 19:317S.Google Scholar
  111. Sofie, E., Riederer, P., Heinsen, H., Beckman, H., Reynolds, G. P., Hebenstreit, G., and Youdim, M. B. H., 1988, Increased iron (III) and total iron content in post mortem substantia nigra of Parkinsonian brain, J. Neural Transm. 74:199–205.CrossRefGoogle Scholar
  112. Tanzi, R. E., and Hyman, B. T., 1991, Alzheimer’s mutation (letter), Nature 350:564.PubMedCrossRefGoogle Scholar
  113. Taylor, E. M., Crowe, A., and Morgan, E. H., 1991, Transferrin and iron uptake by the brain: Effects of altered iron status, J. Neurochem. 57:1584–1592.PubMedCrossRefGoogle Scholar
  114. Thompson, C. M., Marksbery, W. r., Ehmann, W. D., Mao, Y.-X., and Vance, D. E., 1988, Regional brain trace-element studies in Alzheimer’s disease, Neurotoxicology 9:1–9.PubMedGoogle Scholar
  115. Tsutsumi, M., Skinner, M. K., and Sanders-Bush, E., 1989, Transferrin gene expression and synthesis by cultured choroid plexus epithelial cells: Regulation by serotonin and cyclic adenosine 3′,5′-monophosphate, J. Biol. Chem. 264:9626–9631.PubMedGoogle Scholar
  116. Uitti, R. J., Rajput, A. H., Rozdilsky, B., Bickis, M., Wollin, T., and Yuen, W. K., 1989, Regional metal concentrations in Parkinson’s disease and control brains, Can. J. Neurol. Sci. 16:310–314.PubMedGoogle Scholar
  117. Wilson, R., and Tocher, D. R., 1991, Lipid and fatty acid composition is altered in plaque tissue from multiple sclerosis brain compared with normal brain white matter, Lipids 26:9–15.PubMedCrossRefGoogle Scholar
  118. Youdim, M. B. H., Ben-Schachar, D., and Reiderer, P., 1989, Is Parkinson’s disease a progressive siderosis of substantia nigra resulting in iron and melanin-induced neurodegeneration? Acta Neurol. Scand. 126:47–54.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1997

Authors and Affiliations

  • James R. Connor
    • 1
  1. 1.Department of Neuroscience and AnatomyPennsylvania State University College of Medicine, M. S. Hershey Medical CenterHersheyUSA

Personalised recommendations