Endocrine Abstracts

It is well established that thyroid hormones (TH) possess the ability to regulate body temperature. Thermogenesis can be induced peripherally in fat and muscle, but the active hormone T3 can also act centrally in the brain to raise the body temperature via the sympathetic nervous system. In recent studies, T3 treatment in mice has been shown to elevate the body temperature even far below thermoneutrality. This indicates that the induced hyperthyroidism causes a state of pyrexia instead of hyperthermia and the body temperature set point is elevated. However, the brain region where TH can act to alter this body temperature set point is not yet known. Candidate regions have been identified using PET/CT scans of mice undergoing T3 treatment to show neuronal activation. Among them is the Zona Incerta (ZI), a region of the subthalamus, that has previously been indicated in body temperature control, as well as anxiety modulation. Thus, the goal of this research project is to investigate the role of TH signalling of the ZI in the control of body temperature and anxiety. To inhibit TH signalling, an adeno-associated virus expressing a dominant negative thyroid hormone receptor α1 was injected into the ZI using stereotaxic surgery. The results showed tendentially increased anxiety, as could be observed by higher corticosterone serum levels, as well as altered RNA levels of glucocorticoid target genes and an increased R amplitude in ECG. Moreover, inhibition of ZI TH signalling caused decreased body weight gain with no difference in neither food or water intake, nor energy expenditure. Along with an increased body weight loss during fasting, these findings suggest higher stress levels. However, inhibiting TH signalling in the ZI failed to lower the body temperature, as seen by radiotelemetry and infrared camera data. Collectively, the preliminary data gathered from this study indicates that ZI TH signalling contributes to stress and anxiety in mice but does not play a role in body temperature control.