Affiliation:
1. Department of Clinical Pharmacy, Faculty of Pharmacy, Jordan University of Science and Technology, Irbid, Jordan
2. Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, Houston,
TX, USA
Abstract
Background:
The calcium/calmodulin protein kinase II (CaMKII) signaling cascade
is crucial for hippocampus-dependent learning and memory. Hypothyroidism impairs hippocampus-
dependent learning and memory in adult rats, which can be prevented by simple replacement
therapy with L-thyroxine (thyroxine, T4) treatment. In this study, we compared animal models of
hypothyroidism induced by thyroidectomy and treatment with propylthiouracil (PTU) in terms of
synaptic plasticity and the effect on underlying molecular mechanisms of spatial and non-spatial
types of memory.
Methods:
Hypothyroidism was induced using thyroidectomy or treatment with propylthiouracil
(PTU). L-thyroxin was used as replacement therapy. Synaptic plasticity was evaluated using in
vivo electrophysiological recording. Training in the radial arm water maze (RAWM), where rats
had to locate a hidden platform, generated spatial and non-spatial learning and memory. Western
blotting measured signaling molecules in the hippocampal area CA1 area.
Results:
Our findings show that thyroidectomy and PTU models are equally effective, as indicated
by the identical plasma levels of thyroid stimulating hormone (TSH) and T4. The two models
produced an identical degree of inhibition of synaptic plasticity as indicated by depression of
long-term potentiation (LTP). For non-spatial memory, rats were trained to swim to a visible
platform in an open swim field. Analysis of hippocampal area CA1 revealed that training, on
both mazes, of control and thyroxine-treated hypothyroid rats, produced significant increases in
the P-calcium calmodulin kinase II (P-CaMKII), protein kinase-C (PKC), calcineurin and calmodulin
protein levels, but the training failed to induce such increases in untreated thyroidectomized
rats.
Conclusion:
Thyroxine therapy prevented the deleterious effects of hypothyroidism at the molecular
level.
Publisher
Bentham Science Publishers Ltd.
Subject
General Health Professions
Cited by
2 articles.
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