Developmental iodine deficiency delays the maturation of newborn granule neurons associated with downregulation of p35 in postnatal rat hippocampus

Environ Toxicol. 2014 Aug;29(8):847-55. doi: 10.1002/tox.21811. Epub 2012 Sep 15.

Abstract

We evaluated the role of p35 in the maturation of hippocampal granule neurons in offspring caused by developmental iodine deficiency. Two developmental rat models were established with either an iodine-deficient diet, or propylthiouracil-adulterated water (5 ppm) to impair thyroid function, in pregnant rats from gestational day 6 until postnatal day 28. The protein levels of p35, cyclin-dependent kinase 5, β-catenin, and N-cadherin were assessed on postnatal day 14, 21, and 28. Dendritic morphogenesis of newborn granule neurons in dentate gyrus was examined. Developmental hypothyroidism induced by iodine deficiency and PTU treatment delayed the maturation of hippocampal granule neurons in the offspring and decreased the percentage of Dcx-positive neurons that expressed β-catenin on postnatal day 21 and 28. In addition, downregulation of p35 was observed in dentate gyrus of hypothyroid groups. Developmental hypothyroidism induced by iodine deficiency and PTU treatment could delay the maturation of newborn granule neurons in dentate gyrus, and this deficit may be attributed to the downregulation of p35.

Keywords: dentate gyrus; development; granule cell; iodine deficiency; p35.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Dentate Gyrus / growth & development
  • Dentate Gyrus / metabolism
  • Doublecortin Protein
  • Down-Regulation
  • Female
  • Hippocampus / growth & development
  • Hippocampus / metabolism*
  • Hypothyroidism / metabolism
  • Iodine / deficiency*
  • Maternal Exposure
  • Neurons / metabolism*
  • Phosphotransferases / metabolism*
  • Pregnancy
  • Prenatal Exposure Delayed Effects / metabolism
  • Propylthiouracil / toxicity
  • Rats
  • Rats, Wistar

Substances

  • Cdk5r1 protein, rat
  • Dcx protein, rat
  • Doublecortin Protein
  • Propylthiouracil
  • Iodine
  • Phosphotransferases