Developmentally-induced hypothyroidism alters the expression of Egr-1 and Arc genes and the sensitivity to cannabinoid agonists in the hippocampus. Possible implications for memory and learning

Mol Cell Endocrinol. 2013 Jan 5;365(1):119-28. doi: 10.1016/j.mce.2012.10.004. Epub 2012 Oct 16.

Abstract

We analyzed the role of the cannabinoid system in the cognitive deficits caused by developmentally-induced hypothyroidism. We studied in control and hypothyroid rats the effect of a cannabinoid agonist on spatial memory, hippocampal phosphorylation of CREB and expression of early genes. Our results show that, 1-basal hippocampal expression of early genes and spatial learning are decreased in hypothyroid rats; 2-hypothyroid rats are very sensitive to cannabinoid agonists. Low dose of cannabinoid agonist ineffective in controls altered spatial memory, CREB's phosphorylation and early gene expression in hypothyroids. These effects are not due a change in CB1 receptor (CB1R) content. 3-Treatment of hypothyroid rats with thyroid hormones normalized the biochemical and behavioral responses to cannabinoid agonists but did not correct the low basal levels of early gene transcripts and the deficits in spatial learning. All these data suggest that the hippocampal deregulation of early genes expression could play an important role in the basal cognitive deficits of hypothyroid rats.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Behavior, Animal / drug effects
  • Cannabinoid Receptor Agonists / adverse effects
  • Congenital Hypothyroidism / drug therapy
  • Congenital Hypothyroidism / metabolism*
  • Congenital Hypothyroidism / pathology
  • Congenital Hypothyroidism / physiopathology
  • Cytoskeletal Proteins / genetics
  • Cytoskeletal Proteins / metabolism*
  • Disease Models, Animal*
  • Down-Regulation*
  • Drug Resistance / drug effects
  • Early Growth Response Protein 1 / genetics
  • Early Growth Response Protein 1 / metabolism*
  • Endocannabinoids / agonists*
  • Hippocampus / drug effects
  • Hippocampus / metabolism*
  • Hippocampus / pathology
  • Hormone Replacement Therapy
  • Learning Disabilities / chemically induced
  • Learning Disabilities / etiology
  • Learning Disabilities / prevention & control
  • Male
  • Maze Learning / drug effects
  • Memory Disorders / chemically induced
  • Memory Disorders / etiology
  • Memory Disorders / prevention & control
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Neurons / drug effects
  • Neurons / metabolism
  • Neurons / pathology
  • Rats
  • Rats, Wistar
  • Reaction Time / drug effects
  • Spatial Behavior / drug effects
  • Thyroid Hormones / therapeutic use

Substances

  • Cannabinoid Receptor Agonists
  • Cytoskeletal Proteins
  • Early Growth Response Protein 1
  • Egr1 protein, rat
  • Endocannabinoids
  • Nerve Tissue Proteins
  • Thyroid Hormones
  • activity regulated cytoskeletal-associated protein