Prenatal thyroxine treatment promotes anxiolysis in male Swiss mice offspring.

The proper functioning of the maternal thyroid plays a crucial role in fetal development. Thus, the aim of our study was to verify how maternal hyperthyroidism is able to change behavioral parameters in mice offspring during adulthood. For this purpose, pregnant Swiss mice (n = 24 and ~35 g) were randomly assigned into two groups: a control and a thyroxine (T4)-treatment group. The control was treated with 0.9% saline, while the treatment group received T4 (200 µg/kg, s.c.) once daily during the entire pregnancy period. After completing 70 days of life, a part of male offspring underwent a battery of tests, including open field, dark-light box, elevated plus maze, marble burying, rotarod and tail suspension tests. The other male pups were euthanized, being hippocampus and serum collected for RNA analysis and hormones measurement, respectively. Statistical analysis was performed using Student's t-test, and the means were considered significantly different when p < 0.05. In adult offspring, a significant decrease was observed for serum T3 in treated group. It was demonstrated that the T4 group had an increase in total distance traveled in an open field test. In the elevated plus maze test, we observed a higher time in opened arms as well as an increased in percentage of entries in these arms. In the hippocampus, T4 offspring had a higher expression of tryptophan hydroxylase 2 (TPH2), serotonin transporter (SERT) and glutamate decarboxylase 67 (GAD 67) in comparison to controls. These findings suggest that prenatal T4 treatment alters hippocampal serotonergic and GABAergic systems, promoting anxiolysis in male adult offspring.

Sleep deprivation alters thyroid hormone economy in rats.

NEW FINDINGS: What is the central question of this study? The relationship between the thyroid system and sleep deprivation has seldom been assessed in the literature, and mounting evidence exists that sleep disturbances influence human lifestyles. The aim of this study was to investigate the hypothalamic-pituitary-thyroid axis and thyroid hormone metabolism in sleep-deprived and sleep-restricted rats. What is the main finding and its importance? Central hypothyroidism and high thyroxine (T4 ) to 3,5,3'-triiodothyronine (T3 ) activation in brown adipose tissue were observed following sleep deprivation. Sleep-restricted rats exhibited normal thyroid-stimulating hormone and T4 concentrations despite increased circulating T3 . Sleep recovery for 24 h did not normalize the high T3 concentrations, suggesting that high T3 is a powerful counterregulatory mechanism activated following sleep deprivation. Modern life has shortened sleep time, and the consequences of sleep deprivation have been examined in both human subjects and animal models. As the relationship between thyroid function and sleep deprivation has not been fully investigated, the aim of this study was to assess the hypothalamic-pituitary-thyroid axis and thyroid hormone metabolism following paradoxical sleep deprivation (PSD) and sleep restriction (SR) in rats. The effects of a 24 h rebound period were also studied. Male Wistar rats (200-250 g, n = 10 per group) were subjected to sleep deprivation via the modified multiple platform method. Rats were assigned to the following seven groups: control, PSD for 24 or 96 h, 24 or 96 h of sleep deprivation with rebound (PSD24R and PSD96R), SR for 21 days (SR21) and SR21 with rebound (SR21R). Blood samples were collected to determine the 3,5,3'-triiodothyronine (T3 ), thyroxine (T4 ) and thyroid-stimulating hormone concentrations. Brown adipose tissue iodothyronine deiodinase type 2 (D2) activity was also evaluated. Body weight gain was dramatically reduced (by ∼50-100%) in all sleep-deprived and sleep-restricted rats; rebound restored this parameter in only the PSD24R group. The serum TSH and T4 concentrations decreased, whereas T3 increased in both the PSD24 and PSD96 groups compared with control animals (P < 0.05). Only PSD24R and PSD96R normalized T4 and thyroid-stimulating hormone concentrations, respectively, independently of the higher circulating T3 concentrations (∼20-30%) noted in all groups compared with control animals (P < 0.05). Brown adipose tissue D2 activity increased in the PSD 24 and 96 h groups (∼10 times), and PSD24R was more effective than PSD96R at restoring basal brown adipose tissue D2 activity. Our data suggest that thyroid hormone metabolism adapts to sleep deprivation-induced hypothalamic-pituitary-thyroid alterations and increases T4 to T3 activation peripherally, thereby increasing circulating T3 in rats.