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

BMC Neurosci. 2010 Apr 23:11:50. doi: 10.1186/1471-2202-11-50.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Axons / metabolism
  • Axons / pathology
  • Brain Diseases, Metabolic / metabolism
  • Brain Diseases, Metabolic / pathology
  • Brain Diseases, Metabolic / physiopathology
  • Cell Differentiation / physiology
  • Cell Proliferation
  • Disease Models, Animal
  • Doublecortin Domain Proteins
  • Doublecortin Protein
  • Down-Regulation / physiology
  • Hippocampus / growth & development*
  • Hippocampus / metabolism*
  • Hippocampus / physiopathology
  • Hypothyroidism / complications*
  • Iodine / deficiency*
  • Learning Disabilities / etiology
  • Learning Disabilities / metabolism
  • Learning Disabilities / physiopathology
  • Microtubule-Associated Proteins / metabolism*
  • Neural Cell Adhesion Molecules / metabolism*
  • Neurogenesis / physiology
  • Neuropeptides / metabolism*
  • Rats
  • Rats, Wistar
  • Thyroid Hormones / biosynthesis
  • Thyroid Hormones / blood
  • Up-Regulation / physiology

Substances

  • Dcx protein, rat
  • Doublecortin Domain Proteins
  • Doublecortin Protein
  • Microtubule-Associated Proteins
  • Neural Cell Adhesion Molecules
  • Neuropeptides
  • Thyroid Hormones
  • Iodine