Thyroidectomy- And Ptu-Induced Hypothyroidism: Effect of L-Thyroxine on Suppression of Spatial and Non-Spatial Memory Related Signaling Molecules

Abstract The calcium/calmodulin protein kinase II (CaMKII) signaling cascade is crucial for hippocampus-dependent learning and memory. In adult rats, Hypothyroidism impairs hippocampus-dependent learning and memory, 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). 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 model produced identical degree of inhibition of synaptic plasticity as indicated by depression of LTP. We then investigated the effect of thyroidectomy hypothyroidism and thyroxine treatment on the underlying molecular mechanism of spatial and non-spatial types of memory. To generate spatial memory, we used training in the radial arm water maze (RAWM) where rats had to locate a hidden platform. For non-spatial memory, rats were trained to swim to a clearly visible platform in an open swim field. Western blot analysis of hippocampal area CA1 revealed that training, on both mazes, of control and thyroxine-treated hypothyroid rats produced significant increases in the P-CaMKII, PKCγ, calcineurin and calmodulin protein levels, but the training failed to induce such increases in untreated thyroidectomized rats. As expected, we show that thyroxine therapy prevented the deleterious effects of hypothyroidism at the molecular level.