Fetal and neonatal iron deficiency reduces thyroid hormone-responsive gene mRNA levels in the neonatal rat hippocampus and cerebral cortex.
Copper (Cu), iron (Fe), and thyroid hormone (TH) deficiencies produce similar defects in late brain development including hypomyelination of axons and impaired synapse formation and function, suggesting that these micronutrient deficiencies share a common mechanism contributing to these derangements. We previously demonstrated that fetal/neonatal Cu and Fe deficiencies lower circulating TH concentrations in neonatal rats. Fe deficiency also reduces whole-brain T(3) content, suggesting impaired TH action in the developing Fe-deficient brain. We hypothesized that fetal/neonatal Cu and Fe deficiencies will produce mild or moderate TH deficiencies and will impair TH-responsive gene expression in the neonatal cerebral cortex and hippocampus. To test this hypothesis, we rendered pregnant Sprague Dawley rats Cu-, Fe-, or TH-deficient from early gestation through postnatal d 10 (P10). Mild and moderate TH deficiencies were induced by 1 and 3 ppm propylthiouracil treatment, respectively. Cu deficiency did not significantly alter serum or tissue TH concentrations or TH-responsive brain mRNA expression. Fe deficiency significantly lowered P10 serum total T(3) (45%), serum total T(4) (52%), whole brain T(3) (14%), and hippocampal T(3) (18%) concentrations, producing a mild TH deficiency similar to 1 ppm propylthiouracil treatment. Fe deficiency lowered Pvalb, Enpp6, and Mbp mRNA levels in the P10 hippocampus. Fe deficiency also altered Hairless, Dbm, and Dio2 mRNA levels in the P10 cerebral cortex. These results suggest that some of the brain defects associated with Fe deficiency may be mediated through altered thyroidal status and the concomitant alterations in TH-responsive gene transcription.
Department of Pharmacy Practice and Pharmaceutical Sciences, University of Minnesota Duluth, College of Pharmacy, Minnesota 55812, USA.
Thomas W
TW
Bastian
Jeremy A
JA
Anderson
Stephanie J
SJ
Fretham
Joseph R
JR
Prohaska
Michael K
MK
Georgieff
Grant W
GW
Anderson
D000818:Animals; D000831:Animals, Newborn; D002540:Cerebral Cortex / Q000378:metabolism*; D003300:Copper / Q000172:deficiency; D005260:Female; D015870:Gene Expression / Q000235:genetics; D006624:Hippocampus / Q000378:metabolism*; D000090463:Iron Deficiencies; D008297:Male; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D013961:Thyroid Gland / Q000378:metabolism*; D013963:Thyroid Hormones / Q000378:metabolism*
D013963:Thyroid Hormones; D003300:Copper