While iron is essential in living organisms, deficiencies or excesses can lead to pathological conditions such as iron deficiency anemia or hemochromatosis. Consequently, iron metabolism is tightly regulated by several factors. Ferroportin, the sole characterized mammalian iron exporter, and hepcidin, a liver produced peptide capable of degrading ferroportin, has recently been identified in the brain.
In the present study, the effect of development and iron status on ferroportin and hepcidin gene expression in the rat brain was investigated.
In the experiment investigating the effects of development, Wistar rats were killed after 2 weeks, 8 weeks and 8 months. The brain was microdissected into cerebellum, ventral tegmental area (VTA) and habenula.
In the experiment studying the effects of iron status, adult Wistar rats were subjected to iron deficiency ensuring a reduced iron access for the the fetus during the gestational period. The offspring of iron deficient dams were designated into two groups, a treatment group where pups received iron injections and a group receiving saline injections. At the age of 8 weeks, female rats were killed and key organs were harvested. The brain was dissected into samples of cerebral cortex, cerebellum, striatum and brain stem.
The results revealed that aging significantly increased brain iron concentrations with the highest amount in the cerebellum. Ferroportin gene expression in all brain areas declined significantly with aging despite an increase in iron. The presence of hepcidin mRNA in the rat brain was confirmed, however to a minimal extent. Furthermore, age had no significant effect on hepcidin gene expression.
Iron status was shown to have an effect on cerebral cortex iron content, although not significant. Ferroportin gene expression was significantly up regulated in the duodenum of iron deficient rats compared to rats receiving iron supplements. In the liver, ferroportin gene expression was vice versa to that of the duodenum. No significant alteration in ferroportin gene expression was observed in different brain areas of iron deficient, iron reverted and control rats. The level of hepcidin mRNA expression in the liver and duodenum, of rats receiving iron supplements compared to iron deficient rats, was significantly higher. Moreover, hepcidin expression was extremely low in all brain areas investigated despite differences in brain iron level.
In total, iron status and development have some effects on ferroportin and hepcidin gene expression and it seems that other factors, than brain iron content, might influence the expression of key iron transport molecules in the brain.