Immunohistochemical localization of erythropoietin and its receptor in thedeveloping human brain

We have previously shown erythropoietin (Epo) and its receptor (Epo-R) to b e present in the fetal human central nervous system (CNS), and Epo to be pr esent in the spinal fluid of normal preterm and term infants. To investigat e the cellular specificities and developmental patterns of expression of th ese polypeptides in the human brain-areas that have not been well researche d-we designed the following study. Human brains ranging in maturity from 5 weeks post-conception to adult were preserved at the time of elective abort ion, surgical removal (tubal pregnancy, or removal for temporal lobe epilep sy), or autopsy. Immunohistochemistry was used to localize Epo and Epo-R re activity in brains of different stages of development. Astrocytes, neurons, and microglia were identified in sequential tissue sections by specific an tibodies. At 5 to 6 weeks post-conception, both Epo and Epo-R localized to cells in the periventricular,germinal zone. At 10 weeks post-conception, Ep o immunoreactivity was present throughout the cortical wall, with the most intense immunoreactivity present in the ventricular and subventricular zone s. Epo-R, in contrast, was localized primarily to the subventricular zone, with little staining evident in the ventricular zone. In late fetal brains, Epo-R reactivity was most prominent in astrocytic cells, although modest r eactivity was observed in certain neuron populations. In contrast, Epo stai ning localized primarily to neurons in fetal brains, although a subpopulati on of astrocytes was also immunoreactive. In postnatal brains, both astrocy te and neuron populations were immunoreactive with antibodies to Epo-R and Epo. From these results it is clear that Epo and its receptor are present i n the developing human brain as early as 5 weeks post-conception, and each protein shows a specific distribution that changes with development. We spe culate that Epo is important in neurodevelopment, and that it also plays a role in brain homeostasis later in life, functioning in an autocrine or par acrine manner.