Effects of hypothyroidism induced by perinatal exposure to PTU on rat behavior and synaptic gene expression

Toxicology. 2005 Sep 1;212(2-3):135-47. doi: 10.1016/j.tox.2005.04.012.


Hypothyroidism in the rat induced by perinatal exposure to propylthiouracil (PTU) is a useful animal model to study molecular changes underlying neurobehavioral defects associated with this condition. Understanding the developmental alterations in gene expression related to the neurobehavioral dysfunction should help to identify molecular markers for developmental neurotoxicity at an early stage of development. In the present study, we evaluate the effects of PTU on the expression of a set of genes implicated in neural network formation or synaptic function at a minimal dose of PTU causing behavioral alteration. Various doses of PTU were administered to dams from late pregnancy to the lactation period and the expression of selected genes in the hippocampus and the cerebral cortex of offspring was examined by quantitative RT-PCR. Behavioral performance of PTU-treated rats was also assessed. PTU-treated rats showed increased motor activity and impairment of E-maze learning at weaning and after maturation. At doses causing such behavioral alteration, expression of GAP-43 and M1 mRNAs was changed during neuronal network formation, suggesting that levels of these factors during development are important for accurate postnatal development and function.

MeSH terms

  • Acoustic Stimulation
  • Animals
  • Animals, Newborn
  • Antithyroid Agents*
  • Behavior, Animal / drug effects
  • Cerebral Cortex / drug effects
  • Cerebral Cortex / metabolism
  • Female
  • GAP-43 Protein / genetics
  • GAP-43 Protein / metabolism
  • Gene Expression Regulation / drug effects
  • Habituation, Psychophysiologic / drug effects
  • Hippocampus / drug effects
  • Hippocampus / metabolism
  • Hypothyroidism / chemically induced
  • Hypothyroidism / physiopathology*
  • Male
  • Maze Learning / drug effects
  • Motor Activity / drug effects
  • Pregnancy
  • Prenatal Exposure Delayed Effects*
  • Propylthiouracil*
  • Rats
  • Rats, Inbred Strains
  • Receptor, Muscarinic M1 / genetics
  • Receptor, Muscarinic M1 / metabolism
  • Swimming
  • Thyroxine / blood
  • Triiodothyronine / blood


  • Antithyroid Agents
  • GAP-43 Protein
  • Receptor, Muscarinic M1
  • Triiodothyronine
  • Propylthiouracil
  • Thyroxine