The Role of the Hypothalamus in the Seasonal Response to Adenosine A 1 Receptor Agonist‐Induced Hibernation

Abstract

Hibernation is an adaptive strategy characterized by metabolic suppression and a decrease in body temperature (Tb). Arctic Ground Squirrel (AGS) sleep and regulate thermogenesis to enter hibernation. The onset of hibernation can be induced via A1 adenosine receptor agonist (N6-cyclohexyladenosine; CHA). However, this phenomenon occurs only in winter; in summer AGS counteract CHA-induced hibernation restoring Tb after an initial decrease. This phenomenon suggests that a higher order process regulates the seasonal CHA-response, but if it is driven by a winter increase in sleep sensitivity or by a seasonal regulation of thermogenesis is unknown. Hypothalamus controls both sleep and energy homeostasis regulating thermogenesis, in part, via the hypothalamic-pituitary-thyroid (HPT) axis.The intent of this research is to identify the hypothalamic nuclei activated in a seasonally dependent manner in response to CHA-induced hibernation. AGS were treated with CHA or vehicle at different seasonal points (summer and winter) and brains were collected 3h after treatment. Immunohistochemistry was used to localize active nuclei as indicated by cFos-immunoreactivity (rabbit anti-cFos 1:20,000, Sigma) focusing on the nuclei involved in thermoregulation and sleep. Specific markers (e.g. rabbit anti pro-TRH 1:10,000 gift from Eva Redei, rabbit anti-galanin 1:10,000 Millipore) were used to define the phenotype of cFos-ir neurons. Data show similar cFos-ir in the paraventricular nucleus and in the ventrolateral preoptic region of the hypothalamus. These results suggest that mechanisms downstream to hypothalamic modulation of thermogenesis or sleep contribute to the higher order process regulating the seasonal CHA-response.