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NEUROBIOLOGY

Axonal dispatch of iron in neuronal signaling

Nature Chemical Biology volume 15, pages 1135–1136 (2019)Cite this article

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The regulation of brain iron homeostasis, previously thought to be cell autonomous and modulated by local factors in the interstitial fluid, is reported by Wang et al. to be strongly influenced by axonal transport of iron in an activity-dependent and unidirectional manner between functionally associated regions. The supply of iron from the ventral hippocampus to the middle prefrontal cortex subserved an anxiolytic phenotype and mediated the neuropharmacological actions of diazepam and lithium chloride in rodent models.

Levels of iron, the most abundant transition metal in the brain (≈60 mg), increase with age1 and in the context of certain neurological disorders2. Iron is known to be vital for a number of cellular processes, but there has been little prior evidence that iron has a functionally important role in neural signaling and the regulation of behavior. Now, Wang et al.3 provide unexpected but compelling evidence that iron translocates along specific brain axonal projections and that this transport of iron regulates state anxiety. It was not known previously that iron is transported along axons or that neurons could supply their projection regions with a source of iron to impact behavior.

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Fig. 1: Schematic illustration of neuronal activity-dependent iron transport and its psychiatric relevance.

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Affiliations

  1. Department of Neurology and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, P.R. China

    Peng Lei

  2. Melbourne Dementia Research Centre, Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Victoria, Australia

    Peng Lei, Scott Ayton & Ashley I. Bush

Authors
  1. Peng Lei
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  2. Scott Ayton
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  3. Ashley I. Bush
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Correspondence to Peng Lei or Ashley I. Bush.

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Competing interests

A.I.B. is a shareholder in Prana Biotechnology Ltd., Cogstate Ltd., Brighton Biotech LLC, Grunbiotics Pty Ltd., Eucalyptus Pty Ltd., and Mesoblast Ltd. He is a paid consultant for, and has a profit share interest in, Collaborative Medicinal Development Pty Ltd.

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Lei, P., Ayton, S. & Bush, A.I. Axonal dispatch of iron in neuronal signaling. Nat Chem Biol 15, 1135–1136 (2019). https://doi.org/10.1038/s41589-019-0394-3

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