Season Primes the Brain in an Arctic Hibernator to Facilitate Entrance into Torpor Mediated by Adenosine A1 Receptors

Abstract

Torpor in hibernating mammals defines the nadir in mammalian metabolic demand and body temperature that accommodates seasonal periods of reduced energy availability. The mechanism of metabolic suppression during torpor onset is unknown although the central nervous system (CNS) is a key regulator of torpor. Seasonal hibernators such as the arctic ground squirrel (AGS) display torpor only during the winter, hibernation season. The seasonal character of hibernation thus provides a clue to its regulation. In the present study we delivered adenosine receptor agonists and antagonists into the lateral ventricle of AGS at different times of the year while monitoring the rate of O2 consumption and core body temperature as indicators of torpor. The A1 antagonist, cyclopentyltheophylline (CPT) reversed spontaneous entrance into torpor. The adenosine A1 receptor agonist, N6-cyclohexyladenosine (CHA) induced torpor in 6 out of 6 AGS tested during the mid-hibernation season, 2 out of 6 AGS tested early in the hibernation season and none of the 6 AGS tested during the summer, off-season. CHA-induced torpor within the hibernation season was specific to A1AR activation; the A3AR agonist 2-Cl-IB MECA failed to induce torpor and the A2aR antagonist MSX-3, failed to reverse spontaneous onset of torpor. CHA-induced torpor was similar to spontaneous entrance into torpor. These results show that metabolic suppression during torpor onset is regulated within the CNS via A1AR activation and requires a seasonal switch in the sensitivity of purinergic signaling.

Natural Protection Against Cardiac Arrhythmias During Hibernation: Significance of Adenosine

“…Administration of adenosine agonist into the brain induces torpor in arctic ground squirrels (Jinka et al, 2011). By lowering the set-point (T set ) threshold below the actual hypothalamic temperature (T hy ) during entrance into hibernation a smooth entrance is facilitated.…”

“…Core body temperature was measured in an Arctic ground squirrel after arousal from torpor induced by gentle handling and until the animal entered another bout of torpor. Core body temperature and heart rate were measured with an ip transmitter as described previously (Jinka et al, 2011). Torpor in hibernation is broadly divided into three phasesentrance, steady-state, and arousal (Boyer and Barnes, 1999;Carey et al, 2003a;Heldmaier et al, 2004;Drew et al, 2007).…”

“…Changes in core body temperature and whole animal oxygen consumption as measured in an Arctic ground squirrel after arousal from torpor was iniated by gentle handling and until the animal entered another bout of torpor. Core body temperature was measured with an ip transmitter and oxygen consumption was measured using open flow respirometry as described previously (Jinka et al, 2011). The inset illustrates how oxygen consumption precedes a decline in core body temperature during entrance into torpor as shown on a smaller scale.…”

“…Although bears are regarded as hibernators their body temperature does not fall below 30 o C which is above the critical body temperature where ventricular fibrillations are noticed (Johansson, 1984;Eagles et al, 1988;Toien et al, 2011). This chapter discusses about small hibernators in general focusing on the role of nervous system regulation of cardiac function in the light of recent research findings and the importance of adenosine (Miyazawa et al, 2008;Jinka et al, 2011). This chapter gives an overview of hibernation physiology, various mechanisms regulating hibernation, cardiac arrhythmias observed during hibernation, functional difference between hibernator and a non-hibernator, especially in regard to heart function, and finally discusses novel findings and hypothesis that may be translated to treat certain medical conditions such as cardiac arrest and stroke to improve the outcome in such patients.…”

Central adenosine and daily torpor in mice

“…Central (i.e., intracerebroventricular or ICV) activation of this receptor with cyclohexyladenosine (CHA) induces hypothermia and hypometabolism in arctic ground squirrels, but only during the hibernating season suggesting a seasonal regulation of sensitivity to adenosine. 3 Similarly, CHA into the rat, an animal that does not normally engage torpor pathways, induces hypothermia, low heart rate, skipped heart beats, reduced shivering, reduces CO 2 production, and lowers brown fat temperature. 4 Further, blocking adenosine action centrally can both prevent torpor and induce arousal in hamsters.…”