O hipotireoidismo altera a ritmicidade do relógio circadiano central e as oscilações circadianas do perfil de atividade locomotora e temperatura corporal

Abstract

Circadian rhythmicity is defined as a daily oscillation that takes around 24h to complete, and it has been described in many behavioral and physiological parameters like spontaneous locomotor activity (SLA), body temperature (Temp), sleep-wake cycle, hormonal synthesis/secretion, among others. These rhythms are essential for an organism’s survival, and, in mammals, they are spontaneously generated by a hypothalamic neuronal grouping of the suprachiasmatic nucleus, which has as its primordial function the spontaneous generation of circadian rhythmicity, and the synchronization of peripheral molecular clocks, according to temporal clues, which are named zeitgebers (from the German: time clues), being the main one, the photoperiod. Thyroid hormones (HTs) are synthesized in the thyroid gland, and they exert an ample spectrum of functions, including regulation of development, metabolism, and body temperature. Thyroid hypofunction, denominated hypothyroidism, is characterized by low serum levels of HTs, and it corresponds to the world’s second most prevalent endocrinopathy. There’s a correlation between the biological clock and the HTs. The thyroid axis’ hormonal secretion presents circadian rhythmicity, and hypothyroidism alters the molecular clock in peripheral tissues, such as the heart and the anterior pituitary. However, the possible actions of HTs in the central clock are still unknown. This research had as it’s objective the characterization of the possible effects of hypothyroidism on the central circadian clock. For that, C57BL/6J adult male mice were divided into control and hypothyroid groups, which had the daily profiles of the following parameters evaluated: SLA, body temperature, oxygen consumption, genetic expression and neuronal activity of the SCN, as well as the neuronal activity of the preoptic area (POA) and dorsomedial hypothalamus (DMH). SLA and Temp displayed a considerable extension of their daily cycles in free-running hypothyroid animals. Hypothyroidism affects the circadian rhythmicity of genetic expression of the central components of the central clock’s molecular machinery and its neuronal activity. The SCN outputs also had their rhythmicity jeopardized, evidenced by the loss of circadian rhythmicity in oxygen consumption and the neuronal activity pattern of the POA. Therefore, the results of this study suggest that the HTs perform a direct or indirect role in the regulation of activity and rhythmicity of the central circadian clock, impacting the functions regulated by the SCN.