Contribution of Hypothyroidism to Cognitive Impairment and Hippocampal Synaptic Plasticity Regulation in an Animal Model of Depression.

Katarzyna Głombik,Jan Detka,Magdalena Kusek,Bartosz Bobula,Krzysztof Tokarski,Joanna Bąk,Bogusława Budziszewska

doi:10.3390/ijms22041599

Katarzyna Głombik, Jan Detka + Show 5 more

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https://doi.org/10.3390/ijms22041599

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Abstract

The role that thyroid hormone deficiency plays in depression and synaptic plasticity in adults has only begun to be elucidated. This paper analyzes the possible link between depression and hypothyroidism in cognitive function alterations, using Wistar–Kyoto (WKY—an animal model of depression) rats and control Wistar rats under standard and thyroid hormone deficiency conditions (propylthiouracil administration—PTU). A weakening of memory processes in the WKY rats is shown behaviorally, and in the reduction of long-term potentiation (LTP) in the dentate gyrus (DG) and CA1 hippocampal regions. PTU administration decreased LTP and increased basal excitatory transmission in the DG in Wistar rats. A decrease in short-term synaptic plasticity is shown by the paired-pulse ratio measurement, occurring during hypothyroidism in DG and CA1 in WKY rats. Differences between the strains may result from decreases in the p-CaMKII, p-AKT, and the level of acetylcholine, while in the case of the co-occurrence of depression and hypothyroidism, an increase in the p-ERK1-MAP seemed to be important. Obtained results show that thyroid hormones are less involved in the inhibition of glutamate release and/or excitability of the postsynaptic neurons in WKY rats, which may indicate a lower sensitivity of the hippocampus to the action of thyroid hormones in depression.

Highlights

Extensive research has been performed, the etiology of depressive disorder is not fully understood, and the currently available antidepressant drugs are not effective in some patients
The present study demonstrated anxiety-like behaviors, impairment of spatial memory, disturbances in electrophysiological parameters in the CA1 and dentate gyrus (DG) hippocampal regions, and changes in some biochemical markers of neuronal plasticity in the hippocampus in rat models of depression, hypothyroidism, and the co-occurrence of depression and hypothyroidism
Since brain thyroid hormone levels do not correlate with their concentration in the blood, we previously determined the thyroid hormone content in the hippocampus and found that the level of T3 was decreased in Wistar rats receiving PTU and was even more substantially decreased in WKY rats [12]

Summary

Introduction

Extensive research has been performed, the etiology of depressive disorder is not fully understood, and the currently available antidepressant drugs are not effective in some patients. One of the approaches to the therapy of treatment-resistant depression is supportive treatment with thyroid hormones (THs) [1]; the mechanism of action and the roles of these hormones in the pathogenesis of depression are not known This is mainly because the effect of thyroid hormones in the central nervous system in adults is not well-studied. Some studies suggest that in depression, there may be a reduction in the activity, but not necessarily the level of thyroid hormones This is shown by clinical observations indicating that effective therapy of depression with T4 requires higher doses than those used in the treatment of primary thyroid disorders, and in depressed patients, supraphysiological doses of T4 cause fewer side effects than in healthy people [7]. Thyroid hormone content in particular brain regions depends on the expression of their transporters and deiodinases [8]

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