Pellegrino Rosa Maria, Boda Enrica, Montarolo Francesca, Boero Martina, Mezzanotte Mariarosa, Saglio Giuseppe, Buffo Annalisa, Roetto Antonella
Department of Clinical and Biological Sciences, University of Torino, Turin, Italy.
AOU San Luigi Regione Gonzole 10043 Orbassano Turin, Italy.
Sci Rep. 2016 Aug 1;6:30725. doi: 10.1038/srep30725.
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.
转铁蛋白受体2（Tfr2）通过调节铁调节素铁调素（Hepc）来调节全身铁代谢，Tfr2失活会导致全身铁过载。基于证明Tfr2在大脑中表达的数据，我们分析了Tfr2基因敲除小鼠，以研究该组织中Tfr2沉默的分子、组织学和行为后果。Tfr2缺失导致神经组织特定区域铁的积累，且未伴随大脑铁调素反应。此外，Tfr2基因敲除小鼠的边缘回路神经元出现选择性过度激活，并出现类似焦虑的行为。此外，小胶质细胞对铁扰动表现出特别的敏感性。我们得出结论，Tfr2是大脑铁稳态的关键调节因子，并提出Tfr2α在焦虑回路调节中的作用。
