Regulation of iron importers in regions of the central nervous system in iron accumulation models

Abstract

The accumulation of the iron excess in brain is frequently detected in neurodegenerative disorders. Therefore, an understanding of the iron proteins regulation in brain could help for the treatment or prevention of neurodegenerative diseases. Objective: study the effect of iron excess on divalent metal transporter1 (DMT1) and Zrt-Irt-likeProtein14 (ZIP14) expressions in mice brain and in human neuroblastoma cells. Materials and Methods: In vivo studies: CF1 mice(25±5g) were divided into 2 groups (n=6/group;paired design):1)Iron-overload: Fe-Saccharate ip (days0,4,8,12;1800mg/kg),2)Iron-adequate. The Protocol was approved by the Committee on Experimental Animal Use and Care-UNS. In vitro studies: SH-SY5Y cells were treated with FAC30µM/72hs. Immunohistochemistry of mice brain and immunocytochemistry of cells was made for DMT1 and ZIP14. Perl`s staining. Results: Brain: In control mice, DMT1 expression was observed in striatum, hippocampus and cerebellum. In iron-overload, DMT1 expression in striatum, hippocampus and cerebellum was slight respect to control. In cerebellum, DMT1 was strongly expressed in granule cells, with slight immunoreactivity in Purkinje cells of control and iron-overloaded mice. ZIP14 was weakly expressed in striatum, hippocampus and cerebellum in control mice, while, in iron-overload, ZIP14 expression was strong. In cerebellum, ZIP14 was intensely expressed in granule cells and molecular layer control and iron-overloaded mice. Hemosiderin was absent in striatum, hippocampus and cerebellum of control mice, while in iron-overload abundant iron deposit was found. Neuronal cells: DMT1 immunoreactivity was lower in cells with FAC than that observed in control, while ZIP14 was higher. Conclusions: We concluded that iron excess accumulation that occurs in striatum, hippocampus and cerebellum could be the consequence of a high iron uptake produced by the increased ZIP14 expression, while DMT1 would not have a prominent role. In neurons, the increased ZIP14 and decreased DMT1 in iron-overload would suggest that iron importers regulations could be part of a mechanism that would involve cellular control.