Developmental iodine deficiency and hypothyroidism impair neural development in rat hippocampus: involvement of doublecortin and NCAM-180

Abstract

Abstract Background Developmental iodine deficiency results in inadequate thyroid hormone (TH), which damages the hippocampus. Here, we explored the roles of hippocampal doublecortin and neural cell adhesion molecule (NCAM)-180 in developmental iodine deficiency and hypothyroidism. Methods Two developmental rat models were established with either an iodine-deficient diet, or propylthiouracil (PTU)-adulterated water (5 ppm or 15 ppm) to impair thyroid function, in pregnant rats from gestational day 6 until postnatal day (PN) 28. Silver-stained neurons and protein levels of doublecortin and NCAM-180 in several hippocampal subregions were assessed on PN14, PN21, PN28, and PN42. Results The results show that nerve fibers in iodine-deficient and 15 ppm PTU-treated rats were injured on PN28 and PN42. Downregulation of doublecortin and upregulation of NCAM-180 were observed in iodine-deficient and 15 ppm PTU-treated rats from PN14 on. These alterations were irreversible by the restoration of serum TH concentrations on PN42. Conclusion Developmental iodine deficiency and hypothyroidism impair the expression of doublecortin and NCAM-180, leading to nerve fiber malfunction and thus impairments in hippocampal development.