Seasonal changes in adenosine kinase in tanycytes of the Arctic ground squirrel (Urocitellus parryii).

Hibernation is a seasonal strategy to conserve energy, characterized by modified thermoregulation, an increase in sleep pressure and drastic metabolic changes. Glial cells such as astrocytes and tanycytes are the brain metabolic sensors, but it remains unknown whether they contribute to seasonal expression of hibernation. The onset of hibernation is controlled by an undefined endogenous circannual rhythm in which adenosine plays a role through the activation of the A1 adenosine receptor (A1AR). Seasonal changes in brain levels of adenosine may contribute to an increase in A1AR sensitivity leading to the onset of hibernation. The primary regulator of extracellular adenosine concentration is adenosine kinase, which is located in astrocytes. Using immunohistochemistry to localize and quantify adenosine kinase in Arctic ground squirrels' brain collected during different seasons, we report lower expression of adenosine kinase in the third ventricle tanycytes in winter compared to summer; a similar change was not seen in astrocytes. Moreover, for the first time, we describe adenosine kinase expression in tanycyte cell bodies in the hypothalamus and in the area postrema, both brain regions involved in energy homeostasis. Next we describe seasonal changes in tanycyte morphology in the hypothalamus. Although still speculative, our findings contribute to a model whereby adenosine kinase in tanycytes regulates seasonal changes in extracellular concentration of adenosine underling the seasonal expression of hibernation.

Thermoregulation in hibernating mammals: The role of the "thyroid hormones system".

Hibernation is a unique evolutionary adaptation to conserve energy. During the pre-hibernation (i.e. fall) season, a progressive decline in core body temperature and further decrease in metabolism underlie a seasonal modulation in thermoregulation. The onset of hibernation requires marked changes in thermoregulatory attributes including adjustment in body temperature and tissue specific increases in thermogenic capacity. The hibernation season is characterized by a regulated suppression in thermogenesis allowing the onset of torpor interrupted by periodic activation of thermogenesis to sustain interbout arousals. Thyroid hormones are known to regulate both body temperature and metabolism, and for this reason, the hypothalamic-pituitary-thyroid axis and thyroid hormones have been investigated as modulators of thermogenesis in the phenomenon of hibernation, but the mechanisms remain poorly understood. In this review, we present an overview of what is known about the thermogenic roles of thyroid hormones in hibernating species across seasons and within the hibernating season (torpor-interbout arousal cycle). Overall, the hypothalamic-pituitary-thyroid axis and thyroid hormones play a role in the pre-hibernation season to enhance thermogenic capacity. During hibernation, thermogenesis is attenuated at the level of sympathetic premotor neurons within the raphe pallidus and by deiodinase expression in the hypothalamus. Further, as recent work highlights the direct effect of thyroid hormones within the central nervous system in activating thermogenesis, we speculate how similar mechanisms may occur in hibernating species to modulate thermogenesis across seasons and to sustain interbout arousals. However, further experiments are needed to elucidate the role of thyroid hormones in hibernation, moving towards the understanding that thyroid hormones metabolism, transport and availability within tissues may be the most telling indicator of thyroid status.