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Sci Rep. 2016 Aug 1;6:30725. doi: 10.1038/srep30725.

Transferrin Receptor 2 Dependent Alterations of Brain Iron Metabolism Affect Anxiety Circuits in the Mouse.

Author information

1
Department of Clinical and Biological Sciences, University of Torino, Turin, Italy.
2
AOU San Luigi Regione Gonzole 10043 Orbassano Turin, Italy.
3
Department of Neuroscience Rita Levi-Montalcini, University of Torino, Turin, Italy.
4
Neuroscience Institute Cavalieri Ottolenghi Regione Gonzole 10043 Orbassano Turin, Italy.

Abstract

The Transferrin Receptor 2 (Tfr2) modulates systemic iron metabolism through the regulation of iron regulator Hepcidin (Hepc) and Tfr2 inactivation causes systemic iron overload. Based on data demonstrating Tfr2 expression in brain, we analysed Tfr2-KO mice in order to examine the molecular, histological and behavioural consequences of Tfr2 silencing in this tissue. Tfr2 abrogation caused an accumulation of iron in specific districts in the nervous tissue that was not accompanied by a brain Hepc response. Moreover, Tfr2-KO mice presented a selective overactivation of neurons in the limbic circuit and the emergence of an anxious-like behaviour. Furthermore, microglial cells showed a particular sensitivity to iron perturbation. We conclude that Tfr2 is a key regulator of brain iron homeostasis and propose a role for Tfr2 alpha in the regulation of anxiety circuits.

PMID:
27477597
PMCID:
PMC4967901
DOI:
10.1038/srep30725
[Indexed for MEDLINE]
Free PMC Article

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