Early-life iron deficiency alters glucose transporter-1 expression in the adult rodent hippocampus

Background: Early-life iron deficiency (ID) impairs hippocampal energy production. Whether there are changes in glucose transporter (GLUT) expression is not known. Objective: The aim of this study was to investigate whether early-life ID and the treatment iron dose alter brain regional GLUT expression in adult rats and mice. Methods: In Study 1, ID was induced in male and female Sprague Dawley rat pups by feeding dams a 3-mg/kg iron diet during gestation and the first postnatal week, followed by treatment using low-iron [3-10 mg/kg; formerly iron-deficient (FID)-10 group], standard-iron (40-mg/kg; FID-40 group), or high-iron (400-mg/kg; FID-400 group) diets until weaning. The control group received the 40 mg/kg iron diet. GLUT1, GLUT3, hypoxia-inducible factor (HIF)-1α, and prolyl-hydroxylase-2 (PHD2) mRNA and protein expression in the cerebral cortex, hippocampus, striatum, cerebellum, and hypothalamus were determined at adulthood. In Study 2, the role of hippocampal ID in GLUT expression was examined by comparing the Glut1, Glut3, Hif1α, and Phd2 mRNA expression in adult male and female wild-Type (WT) and nonanemic hippocampal iron-deficient and iron-replete dominant negative transferrin receptor 1 (DNTfR1^-/-) transgenic mice. Results: In Study 1, Glut1, Glut3, and Hif1α mRNA, and GLUT1 55-kDa protein expression was upregulated 20-33% in the hippocampus of the FID-10 group but not the FID-40 group, relative to the control group. Hippocampal Glut1 mRNA (-39%) and GLUT1 protein (-30%) expression was suppressed in the FID-400 group, relative to the control group. Glut1 and Glut3 mRNA expression was not altered in the other brain regions in the 3 FID groups. In Study 2, hippocampal Glut1 (+14%) and Hif1α (+147%) expression was upregulated in the iron-deficient DNTfR1^-/- mice, but not in the iron-replete DNTfR1^-/- mice, relative to the WT mice (P < 0.05, all). Conclusions: Early-life ID is associated with altered hippocampal GLUT1 expression in adult rodents. The mouse study suggests that tissue ID is potentially responsible.