Influência do hipotireoidismo sobre o comportamento doentio e a resposta febril durante o desafio imunológico

Abstract

Thyroid hormones are essential to control of multiple functions involved in maintaining homeostasis, including heat production and energy balance processes. Relations between the hypothalamic-pituitary-thyroid axis and immune function are complex and still require further investigation. Sickness behavior is an expression of a motivational state triggered by the activation of the peripheral innate immune system, by which an organism organizes its functions to combat the infection. The aim of this study was to evaluate the influence of thyroid status on behavior responses during endotoxemy. Experimental hypothyroidism was induced by propylthiouracil (PTU) for 30 days (0.05%, added to drinking water). Different doses (100, 200 and 500 ug/Kg) of lipopolysaccharide were tested to evidence sickness behavior. Then, control and treated with PTU mice received a 200ug/Kg LPS dose or saline (ip), and behavioral responses were evaluated for 24 hours. In mice with hypothyroidism PTU-induced were observed an increase in immobility time in the forced swimming (FST), a largest number of hidden balls (MB) and an impairment of memory answers in the long term object recognition tasks (LTM) and water maze Moris (WMM). During the immune challenge, locomotion in the open field (OF) and the floating time in the FST are not modified two hours after LPS administration. However, in the analysis after 24 hours, there was a reduction in locomotor activity, increased floating time, decreased food intake and higher weight loss, learning and memory impairment and also shorter social investigation time in PTU mice. In addition, we observed a lower thermal index and reduction of c-Fos expression in the paraventricular nucleus (PVN) and medial preoptic area (mPOA). These results demonstrate that the thyroid status modifies the behavioral responses to immune challenge, suggesting that the thyroid hormones are essential for the manifestation of sickness behavior during endotoxemy.