A novel model for brain iron uptake: Introducing the concept of regulation

Ian Simpson, Padmavathi Ponnuru, Marianne E. Klinger, Roland L. Myers, Kavi Devraj, Christopher L. Coe, Gabriele R. Lubach, Anthony Carruthers, James Connor

Research output: Contribution to journalArticle

60 Citations (Scopus)

Abstract

Neurologic disorders such as Alzheimer's, Parkinson's disease, and Restless Legs Syndrome involve a loss of brain iron homeostasis. Moreover, iron deficiency is the most prevalent nutritional concern worldwide with many associated cognitive and neural ramifications. Therefore, understanding the mechanisms by which iron enters the brain and how those processes are regulated addresses significant global health issues. The existing paradigm assumes that the endothelial cells (ECs) forming the blood-brain barrier (BBB) serve as a simple conduit for transport of transferrin-bound iron. This concept is a significant oversimplification, at minimum failing to account for the iron needs of the ECs. Using an in vivo model of brain iron deficiency, the Belgrade rat, we show the distribution of transferrin receptors in brain microvasculature is altered in luminal, intracellular, and abluminal membranes dependent on brain iron status. We used a cell culture model of the BBB to show the presence of factors that influence iron release in non-human primate cerebrospinal fluid and conditioned media from astrocytes; specifically apo-transferrin and hepcidin were found to increase and decrease iron release, respectively. These data have been integrated into an interactive model where BBB ECs are central in the regulation of cerebral iron metabolism.

Original languageEnglish (US)
Pages (from-to)48-57
Number of pages10
JournalJournal of Cerebral Blood Flow and Metabolism
Volume35
Issue number1
DOIs
StatePublished - Jan 10 2015

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Iron
Brain
Blood-Brain Barrier
Endothelial Cells
Transferrin
Hepcidins
Restless Legs Syndrome
Intracellular Membranes
Transferrin Receptors
Conditioned Culture Medium
Microvessels
Nervous System Diseases
Astrocytes
Primates
Parkinson Disease
Cerebrospinal Fluid
Alzheimer Disease
Homeostasis
Cell Culture Techniques

All Science Journal Classification (ASJC) codes

  • Neurology
  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine

Cite this

Simpson, Ian ; Ponnuru, Padmavathi ; Klinger, Marianne E. ; Myers, Roland L. ; Devraj, Kavi ; Coe, Christopher L. ; Lubach, Gabriele R. ; Carruthers, Anthony ; Connor, James. / A novel model for brain iron uptake : Introducing the concept of regulation. In: Journal of Cerebral Blood Flow and Metabolism. 2015 ; Vol. 35, No. 1. pp. 48-57.
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Simpson, I, Ponnuru, P, Klinger, ME, Myers, RL, Devraj, K, Coe, CL, Lubach, GR, Carruthers, A & Connor, J 2015, 'A novel model for brain iron uptake: Introducing the concept of regulation', Journal of Cerebral Blood Flow and Metabolism, vol. 35, no. 1, pp. 48-57. https://doi.org/10.1038/jcbfm.2014.168

A novel model for brain iron uptake : Introducing the concept of regulation. / Simpson, Ian; Ponnuru, Padmavathi; Klinger, Marianne E.; Myers, Roland L.; Devraj, Kavi; Coe, Christopher L.; Lubach, Gabriele R.; Carruthers, Anthony; Connor, James.

In: Journal of Cerebral Blood Flow and Metabolism, Vol. 35, No. 1, 10.01.2015, p. 48-57.

Research output: Contribution to journalArticle

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AU - Devraj, Kavi

AU - Coe, Christopher L.

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AU - Carruthers, Anthony

AU - Connor, James

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