Expression of the neuronal transferrin receptor is age dependent and susceptible to iron deficiency.

In order to characterize the mechanism by which Iron (Fe) is taken up by neurons, we examined the neuronal expression of transferrin receptor (TR) in rats during development and iron (Fe) deficiency by using immunohistochemistry, in vitro receptor autoradiography and in situ hybridization. In contrast to the continuous expression of TR in brain capillary endothelial cells regardless of the age of the animals studied, the expression of neuronal TR was almost absent at late embryonic and early postnatal ages but increased with increasing age to reach a plateau from postnatal (P) 21 through adulthood as verified by immunohistochemical staining. Reducing the Fe stores potentiated the expression of TR immunoreactivity in neurons of both young and adult rats in several grey matter regions. Increased TR immunoreactivity was also observed in neuronal extensions of neurons of the medial habenular nucleus, reticular neurons of the brainstem, and fibers projecting to the area postrema. TR immunoreactivity was never observed in white matter regions, except for that recorded in brain capillaries. In vitro receptor autoradiography verified the increased capacity for transferrin binding during Fe deficiency. By contrast, TR mRNA expression was not affected by Fe deficiency. These findings demonstrate that the expression of the neuronal TR protein is age dependent and susceptible to Fe deficiency.