Expression of ferritin protein and subunit mRNAs in normal and iron deficient rat brain

Abstract

In non-neuronal tissue, ferritin subunit mRNAs are regulated by post-transcriptional mechanisms leading to decreased ferritin protein synthesis during iron deficiency. Biochemical studies have demonstrated that the cerebral ferritin concentration declines during iron deficiency, suggesting that expression of ferritin subunit mRNAs in the brain may be regulated by mechanisms similar to those of non-neuronal tissue. However, as ferritin expression has been only vaguely studied in brain, this hypothesis remains to be tested. We investigated the influence of dietary iron deficiency on the cellular distribution of ferritin protein using immunohistochemistry and H- and L-ferritin subunit mRNAs by non-radioactive in situ hybridization. Pregnant rats were subjected to an iron depleted diet (6.4 mg/kg) from the day of conception. Litters were kept on the same diet until euthanized at the postnatal age of 10 weeks. This treatment reduced brain iron levels from approximately 57 to 26 μg/g. Reducing the iron stores reduced histochemical detectable iron and the expression of ferritin immunoreactivity in neurons, oligodendrocyte-like and microglia-like cells. In normal rats, H- and L-ferritin subunit mRNAs were expressed in virtually all neurons and non-neuronal cells. The cerebral expression of the ferritin subunit mRNAs was not affected by iron deficiency. The levels of ferritin subunit mRNAs in the brain were also unaltered from iron deficiency when examined by Northern blotting. In conclusion, brain levels of iron and ferritin protein are highly susceptible to dietary iron deficiency, whereas the cerebral expression of H- and L-ferritin subunit mRNAs remains unchanged.