| Summary: | Hibernation is an adaptive strategy characterized by metabolic suppression and regulation of thermogenesis to maintain energy balance in adverse environmental conditions. Previous study shows the role of adenosine A1 receptor agonist in promoting hibernation in the arctic ground squirrels. N6‐cyclohexyladenosine (CHA), an adenosine A1 receptor agonist, suppresses thermogenesis in a seasonally dependent manner. CHA induces hibernation in winter, while the effect is transient in summer: arctic ground squirrels counteract an initial decrease in metabolism restoring their euthermic values. These observations suggest that a higher order process regulates the seasonal CHA‐response, but if this phenomenon is driven by a seasonal modulation of thermogenesis is not known. The hypothalamus controls 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. Arctic ground squirrels 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 (mouse anti‐cFos 1:20,000, Santa Cruz) focusing on the nuclei involved in thermoregulation and energy homeostasis. Specific markers (e.g. rabbit anti pro‐TRH 1:10,000 gift from Eva Redei) were used to define the phenotype of cFos‐ir neurons. Data show similar cFos‐ir in the paraventricular nucleus. These results suggest that mechanisms downstream to hypothalamic modulation of thermogenesis contribute to the higher order process regulating the seasonal CHA‐response. Support or Funding Information NIH R15NS070779 and Alaska INBRE P20GM103395
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