Attenuation of Hypothyroidism-Induced Cognitive Impairment by Modulating Serotonin Mediation

SIMPLE SUMMARY: Propylthiouracil (PTU) is commonly used to create a model of hypothyroidism, one of the most common diseases worldwide that has a significant social impact. This study aimed to examine the changes in the behavior, cognition, and memory in rats with PTU-induced overt hypothyroidism as well as the effects of tryptophan treatment on this state. For this purpose, we administered 5-OH-tryptophan intraperitoneally or directly into the hippocampus of the hypothyroid animals. Their behavior and cognition were assessed using an open field test, T-maze, and novel object recognition test. There were significant differences in the behavioral patterns of the hypothyroid animals, showing a reduction in locomotor activity, rearing, and memory function compared to the controls. The treatment with 5- hydroxy-tryptophan (5-OH-TRP) alleviated those changes. A staggering amount of research is suggesting that the usual denominators in the pathophysiology of depression and the cognitive decline in hypothyroidism are the hippocampal complex and the distorted serotonin metabolism. In our study, we observed significant beneficial effects on cognitive impairment after 5-OH-TRP administration. Current results are promising and may serve as groundwork for further investigation of functional and structural changes in the hippocampus during a hypothyroid state, and in particular, the effects of serotonin mediation in hypothyroid-associated depressive behavior. ABSTRACT: Thyroid hormones play an important role in the modeling of neural networks in the brain. Besides its metabolic effects, thyroid dysfunction, and hypothyroidism in particular, is frequently associated with cognitive decline and depressive-like behavior. The current study aimed to examine the changes in behavior, cognition, and memory in rats with propylthiouracil-induced overt hypothyroidism. The behavior and cognition were assessed using the open field test, T-maze, and novel object recognition test. We found significant differences in the behavioral patterns of the hypothyroid animals showing a reduction in locomotor activity, frequency of rearing, and impaired memory function compared to the euthyroid controls. As serotonin is an essential biomarker regulating cognition and mood, we tried to modulate the serotonin mediation in hypothyroid animals through tryptophan administration. Treatment with 5-hydroxy-tryptophan (5-OH-TRP) intraperitoneally for 10 days or directly into the hippocampus as a single injection led to attenuation of the hypothyroidism-induced cognitive and memory decline. A staggering amount of research is suggesting that the common denominators in the pathophysiology of depression and the behavior changes in hypothyroidism are the hippocampal complex and the distorted serotonin metabolism. In our study, it was observed a significant alleviation of cognitive impairment and an improvement of memory performance in hypothyroid rats after 5-OH-TRP administration. Current results are promising and may serve as groundwork for further investigation of functional and structural changes in the hippocampus during a hypothyroid state, and in particular, the effects of serotonin mediation in hypothyroid-associated depressive-like behavior.