Experimentally induced hyperthyroidism disrupts hippocampal long-term potentiation in adult rats

Neuroendocrinology. 2011;94(3):218-27. doi: 10.1159/000328513. Epub 2011 Jul 19.

Abstract

Background: Manipulating thyroid hormones has been shown to influence learning and memory. Although a large body of literature is available on the effects of thyroid hormone deficiency on learning and memory functions during developmental or adult-onset hypothyroidism, electrophysiological findings are limited. This limitation is especially notable with respect to thyroxine administration in adult, normothyroid animals.

Methods: Experiments were carried out on 12 adult male Wistar rats, each 9-10 months of age. Rats were randomly divided into hyperthyroid (0.2 mg/kg/day intraperitoneal thyroxine injection, for 21 days) and control groups (n = 6 animals in each group). Following spatial learning performance tests on hyperthyroid and control groups, rats were anesthetized with urethane and placed in a stereotaxic frame. A bipolar, tungsten electrode was used to stimulate the medial perforant path. A glass micropipette was inserted within the granule cell layer of the ipsilateral dentate gyrus to record field excitatory postsynaptic potentials (fEPSP). Following a 15-min baseline recording of fEPSPs, long-term potentiation (LTP) was induced by four sets of tetanic pulse trains.

Results: Thyroxine-treated rats showed significantly worse performance in the spatial memory task and attenuated input-output relationships in the electrophysiological analyses. Treated rats also showed a lower efficacy of LTP induction when compared with controls.

Conclusion: The present study provides clear in vivo evidence for the action of L-thyroxine in the impairment of synaptic plasticity and in inducing spatial memory task deficits in adult rats. These findings may explain the complaints of cognitive function reductions in hyperthyroid patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Animals
  • Behavior, Animal / drug effects
  • Behavior, Animal / physiology
  • Disease Models, Animal
  • Electrophysiological Phenomena / drug effects
  • Hippocampus / drug effects*
  • Hippocampus / physiology
  • Hyperthyroidism / blood
  • Hyperthyroidism / chemically induced*
  • Hyperthyroidism / physiopathology*
  • Long-Term Potentiation / drug effects*
  • Long-Term Potentiation / physiology
  • Male
  • Maze Learning / drug effects
  • Maze Learning / physiology
  • Memory Disorders / blood
  • Memory Disorders / chemically induced
  • Memory Disorders / physiopathology
  • Rats
  • Rats, Wistar
  • Thyroid Hormones / blood
  • Thyroxine / adverse effects*
  • Thyroxine / pharmacology

Substances

  • Thyroid Hormones
  • Thyroxine