A morphological study of the developmentally regulated transport of iron into the brain

The distribution of transferrin, transferrin receptor, ferritin and ferric iron was studied in the developing rat brain. Transferrin immunoreactivity (IR) was observed diffusely in the brain from E16 until P10 from where it gradually decreased. The subcellular distribution of transferrin-IR in neurons was compatible with receptor-mediated uptake from P21 and onwards. Transferrin receptor-IR was observed prenatally on cells of neuroectodermal origin in the ventricular zone and in brain capillary endothelial cells (BCECs). In postnatal rats, transferrin receptor-IR in BCECs was most pronounced in rats aged P10-P21 but thereafter decreased in intensity. The neuronal transferrin-receptor IR in postnatal brains was not consistently expressed on neurons until from P21 and onwards. Transferrin receptor-IR was not observed in astrocytes, oligodendrocytes or ramified microglial cells at any age. Ferric iron and ferritin were present in BCECs already from E16, declined from P3-P5, and was absent by P10. There results are discussed with emphasis on the age-dependent transport of transferrin into the developing brain. The upregulated expression of transferrin receptors on BCECs in the second and third postnatal week is compatible with a high need for iron at this age. The neuronal transferrin receptor expression by P21 coincides with a drop in transferrin-IR and iron transport into the brain at this age, suggesting that neuronal transferrin receptor mRNA is posttranscriptionally regulated by the lowered iron availability from this developmental stage onwards.