Neonatal mouse hippocampus: phlebotomy-induced anemia diminishes and treatment with erythropoietin partially rescues mammalian target of rapamycin signaling

Background Phlebotomy-induced anemia (PIA) is common in premature infants and affects neurodevelopment. PIA alters hippocampal metabolism in neonatal mice through tissue hypoxia and iron deficiency. The mammalian target of rapamycin (mTOR) pathway senses the status of critical metabolites (e.g., oxygen, iron), thereby regulating hippocampal growth and function. We determined the effect of PIA and recombinant human erythropoietin (rHuEpo) treatment on mTOR signaling and expression of genes related to mTOR pathway functions. Methods Mice receiving an iron-supplemented diet were phlebotomized from postnatal day (P)3 to a target hematocrit of