Intracerebral Expression of Transferrin Receptors in Iron-Deficient Rats

  • T. Moos
  • T. M. Hansen
Part of the Advances in Behavioral Biology book series (ABBI, volume 46)


In iron-deprived animals, transferrin receptors were increasingly expressed in both capillary endothelium and choroid plexus epithelium. Transferrin receptors were also increasingly expressed in neurons. It is very likely that this principal distribution is also seen in other mammals, including man. Prospective physiological studies on iron-homeostasis should account for the ability of neurons to internalize iron-transferrin complexes by receptor-mediated endocytosis. The results are important in the context of current therapies for treatment of brain tumors using conjugation of chemotherapeutics to transferrin or transferrin receptor antibodies, as toxin-conjugated transferrin may have the potential of harming normal neurons expressing the transferrin receptor. Moreover, the fact that neurons hallmark transferrin receptors may open new vistas on the role of an impaired intracerebral iron-homeostasis for formation of neurodegenerative disorders.


Transferrin Receptor Brain Capillary Endothelial Cell Small Intestine Epithelium Transferrin Receptor Expression Panum Institute 
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.


Chez les animaux carencés en fer, les récepteurs à la transferrine sont plus fortement exprimés à la fois dans l’endothélium capillaire et dans l’épithélium du plexus choroïde; cette augmentation est également mise en évidence au niveau des neurones. Il est très vraisemblable que cette répartition est la même chez d’autres mammifères, dont l’Homme.Des études physiologiques prospectives sur l’hémostase du fer devraient montrer la capacité des neurones à internaliser les complexes fer-transferrine par endocytose médiée par des récepteurs. Les résultats sont importants dans le contexte des thérapies courantes pour le traitement des tumeurs cérébrales, en conjuguant des produits de chimiothérapie avec la transferrine, ou avec des anticorps dirigés contre le récepteur de la transferrine, car la transferrine conjuguée à un toxique pourrait avoir un effet néfaste sur les neurones normaux qui expriment le récepteur de la transferrine. De plus, le fait que les neurones contrölent les récepteurs à la transferrine peut ouvrir une autre vision du rôle d’une hémostase intracérébrale anormale du fer sur l’apparition des désordres neuro-dégénératifs.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Bloch B, Popovici T, Chouham S, Levin MJ, Tuil D, Kahn A (1987) Transferrin gene expression in choroid plexus of the adult rat brain. Brain Res Bull 18: 573–576PubMedCrossRefGoogle Scholar
  2. Bloch B, Popovici T, Levin MJ, Tuil D, Kahn A (1985) Transferrin gene expression visualized in oligodendrocytes of the rat brain by using in situ hybridization and immunocytochemistry. Proc Natl Acad Sci, USA 82: 6706–6710Google Scholar
  3. Crowe A, Morgan EH (1992) Iron and transferrin uptake by brain and cerebrospinal fluid in the rat. Brain Res 592: 8–16PubMedCrossRefGoogle Scholar
  4. Giometto B, Bozza F, Argentiero V, Gallo P, Pagni S, Piccinno MG, Tavolato B (1990) Transferrin receptors in the rat central nervous system. J Neurol Sci 98: 81–90PubMedCrossRefGoogle Scholar
  5. Graeber MB, Raivich G, Kreutzberg GW (1989) Increase of transferrin receptors and iron uptake in regenerating motor neurons. J Neurosci Res 23: 342–345PubMedCrossRefGoogle Scholar
  6. Huebers HA, Finch CA (1987) The physiology of transferrin and transferrin receptors. Physiol Rev 67: 520–582PubMedGoogle Scholar
  7. Jeffries WA, Brandon MR, Hunt SV, Williams AF, Gatter KC, Mason DY (1984) Transferrin receptor on endothelium of brain capillaries. Nature 312: 162–163CrossRefGoogle Scholar
  8. Laske DW, Ilercil O, Akbasak A, Youle RJ, Oldfield EH (1994) Efficacy of direct intratumoral therapy with targeted protein toxins for solid human gliomas in nude mice. J Neurosurg 80: 520–526PubMedCrossRefGoogle Scholar
  9. Martell LA, Agrawal A, Ross DA, Muraszko KM (1993) Efficacy of transferrin receptor-targeted immunotoxins in brain tumor cell lines and pediatric brain tumors. Cancer Res 53: 1348–1353PubMedGoogle Scholar
  10. Moos T (1995a) Age-dependent retrograde axonal transport of exogenous albumin and transferrin in rat motor neurons. Brain Res 672: 14–23PubMedCrossRefGoogle Scholar
  11. Moos T (1995b) Immunohistochemical Localization of Intraneuronal Transferrin Receptor Immunoreactivity in the Adult Mouse Central Nervous System. SubmittedGoogle Scholar
  12. Moos T (1995c) Developmental profile of non-heme iron distribution in the rat during ontogenesis. Dev Brain Res 87: 203–213CrossRefGoogle Scholar
  13. Moos T, Bayer PE (1995) Detection of plasma proteins in CNS neurons: Conspicuous influence of tissue-processing parameters and the utilization of serum for blocking non-specific reactions. SubmittedGoogle Scholar
  14. Morgan EH (1995) Iron metabolism and transport. In: D. Zakim and T. Bayer (eds): Hepatology. A textbook of liver disease, 3“d edition. Philadelphia: SaundersGoogle Scholar
  15. Morris CM, Candy JM, Bloxham CA, Edwardson JA (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: 158–172PubMedCrossRefGoogle Scholar
  16. Morris CM, Keith AB, Edwardson JA, Pullen RGL (1992b) Uptake and distribution of iron and transferrin in the adult rat brain. J Neurochem 59: 300–306PubMedCrossRefGoogle Scholar
  17. Roberts RL, Fine RE, Sandra A (1993) Receptor-mediated endocytosis of transferrin at the blood-brain barrier. J Cell Sci 104: 521–532PubMedGoogle Scholar
  18. Taylor EM, Crowe A, Morgan EH (1991) Transferrin and iron uptake by the brain: Effects of altered iron status. J Neurochem 57: 1584–1592Google Scholar
  19. Wong-Riley M (1979) Changes in the visual system of monocularly sutured or enucleated cats demonstrable with cytochrome oxidase histochemistry. Brain Res 171: 11–28PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1996

Authors and Affiliations

  • T. Moos
    • 1
  • T. M. Hansen
    • 1
  1. 1.Institute of Medical Anatomy, Section A The Panum InstituteUniversity of CopenhagenDenmark

Personalised recommendations