SpringerLink
Log in

Evidence for Iron Mismanagement in the Brain in Neurological Disorders

  • Chapter
Metals and Oxidative Damage in Neurological Disorders

  • 100 Accesses

Abstract

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).

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Chapter
EUR 29.95
Price includes VAT (Spain)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
EUR 160.49
Price includes VAT (Spain)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
EUR 207.99
Price includes VAT (Spain)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free ship** worldwide - see info
Hardcover Book
EUR 207.99
Price includes VAT (Spain)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free ship** worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Similar content being viewed by others

References

  • 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.

    PubMed  CAS  Google Scholar 

  • 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.

    PubMed  CAS  Google Scholar 

  • 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.

    PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • Baynes, R. D., and Bothwell, T. H., 1991, Iron deficiency, Ann. Rev. Nutr. 11:133–48.

    Google Scholar 

  • Beard, J. L., Connor, J. R., and Jones, B. C., 1993, Iron in the brain, Nutr. Rev. 51:157–170.

    Article  PubMed  CAS  Google Scholar 

  • Benkovic, S., and Connor, J. R., 1993, Ferritin, transferrin and iron in normal and aged rat brains, J. Comp. Neurol. 338:97–113.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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 

  • 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.

    Article  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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 

  • Cairo, G., and Pietrangelo, A., 1994, Transferrin receptor gene expression during rat liver regeneration, J. Biol. Chem. 269:6405–6409.

    PubMed  CAS  Google Scholar 

  • Cammer, W., 1984, Oligodendrocyte associated enzymes, in: Oligodendroglia (W. T. Norton, ed.), Plenum Press, New York, pp. 199–232.

    Google Scholar 

  • Chen, Q., Connor, J. R., and Beard, J. L., 1995, Brain iron, transferrin and ferritin concentrations are altered in develo** iron-deficient rats, J. Nutr. 125:1529–1535.

    PubMed  CAS  Google Scholar 

  • 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.

    Chapter  Google Scholar 

  • Connor, J. R., 1994, Iron acquisition and expression of iron regulatory proteins in the develo** brain: Manipulation by ethanol exposure, iron deprivation and cellular dysfunction, Dev. Neurosci. 16:233–247.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • Connor, J. R., and Menzies, S. L., 1995, Cellular management of iron in the brain, J. Neurol. Sci. 134:33–44.

    Article  PubMed  CAS  Google Scholar 

  • Connor, J. R., and Menzies, S. L., 1996, Relationship of iron to oligodendrocytes and myelination, Glia 17:83–93.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • Connor, J. R., Pavlick, G., Karli, D., Menzies, S. L., and Palmer, C., 1995a, A histochemical study of iron-positive cells in the develo** rat brain, J. Comp. Neurol. 355:111–123.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • Crowe, A., and Morgan, E. H., 1992, Iron and transferrin uptake by brain and cerebrospinal fluid in the rat, Brain Res. 592:8–16.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • Dickinson, T. K., and Connor, J. R., 1994, Histological analysis of selected brain regions of the hypotransferrinemic mouse, Brain Res. 635:169–178.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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 

  • Dwork, A. J., 1994, Effects of diet and development upon the uptake and distribution of cerebral iron, J. Neurol. Sci. 134(supplement):45–51.

    Article  Google Scholar 

  • Dwork, A. J., Schon, E. A., and Herbert, J., 1988, Nonidentical distribution of transferrin and iron in human brain, Neuroscience 27:333–335.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    CAS  Google Scholar 

  • Elovaara, I., Icen, A., Palo, J., and Erkinjuntti, T., 1985, CSF in Alzheimer’s disease, J. Neurol Sci. 70:73–80.

    Article  PubMed  CAS  Google Scholar 

  • 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 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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 

  • 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.

    PubMed  CAS  Google Scholar 

  • Hallgren, B., and Sourander, P., 1958, The effect of age on the nonhaemin iron in the human brain, J. Neurochem. 3:41–51.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    PubMed  CAS  Google Scholar 

  • Hill, J. M., and Swizter, R. C., 1984, The regional distribution and cellular localization of iron in the rat brain, Neuroscience 11:595–603.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • Hu, J., and Connor, J. R., 1996, Characterization of the iron regulatory protein in the human brain, J. Neurochem. 67:838–844.

    Article  PubMed  CAS  Google Scholar 

  • 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 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Chapter  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • Kaneko, Y, Kitamoto, T., Tateosjo, J., and Yamaguchi, K., 1989, Ferritin immunohistochemistry as a marker for microglia, Acta Neuropathol. 79:129–136.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • Koeppen, A., 1995, The history of iron in the brain, J. Neurol. Sci. 134(supplement): 1–9.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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 

  • 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.

    PubMed  CAS  Google Scholar 

  • 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.

    Article  Google Scholar 

  • Levine, S. M., 1991, Oligodendrocytes and myelin sheaths in normal, quaking and shiverer brains are enriched in iron, J. Neurosci. Res. 29:413–419.

    Article  PubMed  CAS  Google Scholar 

  • Levine, S. M., 1992, The role of reactive oxygen species in the pathogenesis of multiple sclerosis, Med. Hypoth. 39:271–274.

    Article  CAS  Google Scholar 

  • 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.

    Article  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • Manges, K., and Connor, J. R., 1996, Heavy chain ferritin binds DNA, Soc. Neurosci. Abstr. 22(1):529.

    Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • Moos, T., 1995a, Increased accumulation of transferrin by motor neurons of the mouse mutant progressive motor neuronopathy (pmn/pmn), J. Neurocytol 24:389–398.

    Article  PubMed  CAS  Google Scholar 

  • Moos, T., 1995b, Age-dependent uptake and retrograde axonal transport of endogenous albumin and transferrin in rat motor neurons, Brain Res. 672:14–23.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  Google Scholar 

  • 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.

    PubMed  CAS  Google Scholar 

  • 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.

    CAS  Google Scholar 

  • 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 

  • Pollitt, E., and Ponpon, I., 1993, Reversal of developmental delays in iron-deficient anaemic infants treated with iron, Lancet 341:1–4.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  Google Scholar 

  • Reif, D. W., and Simmons, R. D., 1990, Nitric oxide mediates iron release from ferritin, Arch. Biochem. Biophys. 283:537–541.

    Article  PubMed  CAS  Google Scholar 

  • 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 

  • Roskams, A. J. I., and Connor, J. R., 1992, The transferrin receptor in the myelin deficient (md) rat, J. Neurosci. Res. 31:421–427.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    PubMed  CAS  Google Scholar 

  • 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 

  • Simpson, R. J., Raja, K. B., Halliwell, B., Evans, P. J., Aruoma, O. I., and Kon**, A. M., 1991, Iron speciation in hypotransferrinemic mouse serum, Biochem. Soc. Trans. 19:317S.

    Google Scholar 

  • 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.

    Article  Google Scholar 

  • Tanzi, R. E., and Hyman, B. T., 1991, Alzheimer’s mutation (letter), Nature 350:564.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    PubMed  CAS  Google Scholar 

  • 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.

    PubMed  CAS  Google Scholar 

  • 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.

    PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Neuroscience and Anatomy, Pennsylvania State University College of Medicine, M. S. Hershey Medical Center, Hershey, Pennsylvania, 17033, USA

    James R. Connor

Authors
  1. James R. Connor
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Pennsylvania State University, Hershey, Pennsylvania, USA

    James R. Connor

Rights and permissions

Reprints and permissions

Copyright information

© 1997 Springer Science+Business Media New York

About this chapter

Cite this chapter

Connor, J.R. (1997). Evidence for Iron Mismanagement in the Brain in Neurological Disorders. In: Connor, J.R. (eds) Metals and Oxidative Damage in Neurological Disorders. Springer, Boston, MA. https://doi.org/10.1007/978-1-4899-0197-2_2

Download citation

  • DOI: https://doi.org/10.1007/978-1-4899-0197-2_2

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4899-0199-6

  • Online ISBN: 978-1-4899-0197-2

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation