Seasonal decrease in thermogenesis and increase in vasoconstriction explain seasonal response to N⁶‐cyclohexyladenosine‐induced hibernation in the Arctic ground squirrel (Urocitellus parryii)

Abstract

Hibernation is a seasonal phenomenon characterized by a drop in metabolic rate and body temperature. Adenosine A1 receptor agonists promote hibernation in different mammalian species, and the understanding of the mechanism inducing hibernation will inform clinical strategies to manipulate metabolic demand that are fundamental to conditions such as obesity, metabolic syndrome, and therapeutic hypothermia. Adenosine A1 receptor agonist‐induced hibernation in Arctic ground squirrels is regulated by an endogenous circannual (seasonal) rhythm. This study aims to identify the neuronal mechanism underlying the seasonal difference in response to the adenosine A1 receptor agonist. Arctic ground squirrels were implanted with body temperature transmitters and housed at constant ambient temperature (2°C) and light cycle (4L:20D). We administered CHA (N6‐cyclohexyladenosine), an adenosine A1 receptor agonist in euthermic‐summer phenotype and euthermic‐winter phenotype and used cFos and phenotypic immunoreactivity to identify cell groups affected by season and treatment. We observed lower core and subcutaneous temperature in winter animals and CHA produced a hibernation‐like response in winter, but not in summer. cFos‐ir was greater in the median preoptic nucleus and the raphe pallidus in summer after CHA. CHA administration also resulted in enhanced cFos‐ir in the nucleus tractus solitarius and decreased cFos‐ir in the tuberomammillary nucleus in both seasons. In winter, cFos‐ir was greater in the supraoptic nucleus and lower in the raphe pallidus than in summer. The seasonal decrease in the thermogenic response to CHA and the seasonal increase in vasoconstriction, assessed by subcutaneous temperature, reflect the endogenous seasonal modulation of the thermoregulatory systems necessary for CHA‐induced hibernation. Cover Image for this issue: doi: .

Omega 3 fatty acids stimulate thermogenesis during torpor in the Arctic Ground Squirrel

“…During the pre-hibernation feed period, waxed and sterilized I-button temperature loggers (DS1922L-F5 temperature accuracy from − 10 to + 65 °C, resolution ± 0.5 °C, Maxim Integrated, San Jose, CA) were implanted in the abdominal cavity using sterile technique as previously described 66 . Loggers were recovered after tissue collection in winter and temperature data were downloaded.…”

“…During the hibernation season, the “shavings added” method was employed to track torpor bout length 66 . On the first day of torpor when respirations were below 5 breaths per minute and the animal was inactive and showed a curled posture, shavings were placed onto the animals’ back.…”

Iodine Redistribution During Trauma, Sepsis, and Hibernation: An Evolutionarily Conserved Response to Severe Stress

“…Care was taken to minimize all disturbances in the hibernation chamber during the hibernation season, and access was restricted. Animals were implanted with iButton temperature loggers (Maxim Integrated, San Jose, CA) using sterile technique in the abdominal cavity as previously described ( 30 ). Euthermic animals were anesthetized with 5% isoflurane and maintained at 3% mixed with 100% medical grade oxygen delivered at a flow rate of 1.5 L/min; torpid animals did not require anesthesia.…”

Characterization and Seasonal Modulation of Adenosine A1 Receptors in the Arctic Ground Squirrel Brain

“…Stimulation of A 1 AR within the CNS is necessary for the onset of torpor in hibernating Arctic Ground Squirrels (AGS; Urocitellus parryii) ; however, the response is regulated by a process entrained to a circannual rhythm that governs seasonal sensitivity to the A 1 AR agonist N 6 -cyclohexyladenosine (CHA). Evidence from our laboratory suggests that the winter season enhances the influence of CHA on thermogenesis within the median preoptic nucleus and the rostral raphe pallidus to inhibit the premotor sympathetic neurons within the rPA that drive thermogenesis [ 5 ]. The mechanism underlying seasonal sensitivity to CHA is unknown but may involve changes in adenosinergic tone within thermoregulatory nuclei in the hypothalamus or changes at the level of the A 1 AR.…”