Endocrine Abstracts

Objective: Thyroid hormones are required not only for central nervous system development in the early stages of life but also play a key role in the maintenance of adult brain function. It is known that in adults, thyroid diseases can lead to various clinical manifestations i.e affective disorders, depression, memory impairment. The effects of hypothyroidism on brain functions seem particularly pronounced in depression, but until now, the mechanism underlying this relationship has not been fully understood.

Aim: The goal of the present study was to determine the effects of hypothyroidism on the brain glycolysis, citric acid cycle and oxidative phosphorylation processes in an animal model of depression.

Methods: Study was performed in an animal model of endogenous depression (Wistar-Kyoto rats) and model of coexistent depression and hypothyroidism (6-n-propyl-2-thiouracil – PTU- treatment). PTU (0.05%) was administered in drinking water for 3 weeks. The behavioral tests, enzyme-linked immunosorbent assays, colorimetric methods, immunoblots, and high-resolution respirometry were applied to investigate the changes in selected metabolic markers in the frontal cortex and hippocampus. After behavioral verification animals were sacrificed under nonstressful conditionsto dissect frontal cortices and hippocampi. The results were analyzed using the STATISTICA 13.3 software. A p-value <0.05 was considered to be significant.

Results: The applied model was verified behaviorally and hormonally. It was observed that in the model of co-occurrence of depression and hypothyroidism the pyruvate concentrations in the frontal cortex and hippocampus were downregulated and the lactate level in the hippocampus was reduced. Moreover, in the hippocampus, the aconitase activity was increased. The levels of electron transport chain complexes and pyruvate dehydrogenase activity in the frontal cortex were reduced. In the functional study, conducted with high-resolution respirometry the alternations in the oxidative phosphorylation processes in the hippocampus were demonstrated.

Conclusions: Obtained data indicate an important impact of thyroid hormones on brain metabolism in the course of depression. Furthermore, the hypothalamic-pituitary-thyroid axis hypoactivity increases brain metabolic changes observed in the model of endogenous depression. Changes in the frontal cortex may result from an observed decrease in the expression of thyroid hormone receptor alpha-1 and/or D2 deiodinase downregulation. It also seems that metabolic changes in the hippocampus may be one of the causes of long-term potentiation reduction and synaptic plasticity impairment.

Acknowledgments: This work was supported by grant no. 2017/25/B/NZ7/01708 National Science Centre, Poland.