Elsevier

Brain Research

Volume 592, Issues 1–2, 2 October 1992, Pages 8-16
Brain Research

Research report
Iron and transferrrin uptake by brain and cerebrospinal fluid in the rat

https://doi.org/10.1016/0006-8993(92)91652-UGet rights and content

Abstract

Iron and transferrin uptake into the brain, CSF and choroid plexus, and albumin uptake into the CSF and choroid plexus, were determined after the intravenous injection of [59Fe-125]Itransferrin and [131I]albumin into control rats aged 15, 21 and 63 days and 21-day iron-deficient rats. Iron uptake by the brain was unidirectional, greatly exceeded that of transferrin and was equivalent to 39 and 36% of the plasma iron pool per day in the 15-day control and 21-day iron-deficient rats. The rate of transferrin catabolism in the rats was only about 20% of the plasma pool per day. Iron and transferrin uptake into the brain and CSF decreased with increasing age and was greater in the iron-deficient than in the control 21-day rats. The quantity of 125I-transferrin recovered in the CSF could account for only a small proportion of the iron taken up by the brain. Albumin transfer to the CSF also decreased with age but was lower than that of transferrin and was not affected by iron deficiency. Similarly, the plasma: CSF concentration ratios of transferrin and albumin, as determined immunologically, decreased with age and were greater for transferrin than albumin. It is concluded that iron uptake by the brain is dependent on iron release from transferrin at the cerebral capillary endothelial cells with recycling of transferrin to the plasma and transfer of the iron into the brain interstitium. Only a small fraction of the transferrin bound by brain capillaries is transcytosed into the brain and CSF, this being one source of CSF transferrin while other sources are local synthesis and transfer from the plasma by the choroid plexuses.

References (32)

  • K. Thorstensen et al.

    Uptake of iron from transferrin by isolated rat hepatocytes. A redox-mediated plasma membrane process?

    J. Biol. Chem.

    (1988)
  • D. Trinder et al.

    The effects of an antibody to the rat transferrin receptor and of rat serum of albumin on the uptake of diferric transferrin by rat hepatocytes

    Biochim. Biophys. Acta

    (1988)
  • B. Van Deurs

    Vesicular transport of horseradish peroxidase from brain to blood in segments of the cerebral microvasculature in adult mice

    Brain Res.

    (1977)
  • A.R. Alred et al.

    Distribution of transferrin synthesis in brain and other tissues in the rat

    J. Biol. Chem.

    (1987)
  • O. Amtorp

    Transfer of I125-albumin from blood into brain and cerebrospinal fluid in the newborn and juvenile rats

    Acta Physiol. Scand.

    (1976)
  • R.D. Broadwell et al.

    Brain-blood barrier? Yes and no

  • Cited by (141)

    • Role of endolysosome function in iron metabolism and brain carcinogenesis

      2021, Seminars in Cancer Biology
      Citation Excerpt :

      Despite the presence of iron binding proteins and export systems, incubation of cells with Fe3+ results in increases in the intracellular labile iron pool and oxidative damage [105,106]. While most cells can regulate levels of iron by cell division, neurons are post-mitotic cells and must rely on iron homeostatic mechanisms to avoid iron-induced oxidative stress [105], including downregulating the expression of TfR [107,108]. Neurons can also control levels of iron at the molecular level via post-transcriptional modification by iron regulatory proteins (IRP1 and IRP2).

    • Designing peptide nanoparticles for efficient brain delivery

      2020, Advanced Drug Delivery Reviews
      Citation Excerpt :

      A cognate ligand for the TfR is the iron binding protein Tf, which is a transmembrane glycoprotein consisting of two 90 kDa subunits, linked by intermolecular disulfide bonds and with each subunit binding to one molecule of Tf [183]. Although Tf is a specific ligand to TfR, Tf is a questionable targeting moiety for drug delivery, mainly due to the fact that only a small amount of Tf is transcytosed across the BECs [184,185]. Thus, monoclonal antibodies against the TfR, which bind to epitopes on the extracellular domain of TfR distal to the Tf binding side circumventing competition with endogenous Tf, have been widely developed for RMT-based delivery [186,187].

    • Striking while the iron is hot: Iron metabolism and ferroptosis in neurodegeneration

      2019, Free Radical Biology and Medicine
      Citation Excerpt :

      This model is supported by the observation that cultured bovine BCECs cycle Tf-TfR1 complexes and that holo-Tf transported across these cells may not undergo intraendothelial degradation [47,174]. However no evidence has emerged to demonstrate the transport of Tf from the systemic circulation across BCECs into the brain [43,150,202]. Astrocytes are essential support cells in the neurovascular unit and serve to release the iron supplied by BCECs to the neurons while mitigating iron toxicity [1,23].

    • Regulatory mechanisms for iron transport across the blood-brain barrier

      2017, Biochemical and Biophysical Research Communications
      Citation Excerpt :

      The identification of the mechanism by which apo-Tf induces iron release from endothelial cells, that may involve synergistic interaction with hepcidin, is perhaps the critical step to understanding regional control of brain iron uptake. In conclusion, these data not only provide further support for a DMT1-dependent endocytic process mediating the passage of iron across the endothelial cells that constitute the BBB but addresses a long-observed enigma in the field; namely, the disproportionately greater transport of iron relative to Tf into the brain [24,26,27,38,42–45]. We propose that the levels of apo-Tf and iron delivered to the brain are tightly regulated by the ratio of apo-Tf:holo-Tf in conjunction with hepcidin in the extracellular fluid of each brain region.

    View all citing articles on Scopus
    View full text