Neurochemical Pathways Involved in A 1 Adenosine Receptor Agonist‐Induced Hibernation in the Arctic Ground Squirrel ( Urocitellus parryii)

• Published in: The FASEB Journal
• Main Authors: Jenkins, Mackenzie, Frare, Carla, Drew, Kelly
• Other Authors: National Institutes of Health, National Science Foundation
• Format: Article in Journal/Newspaper
• Language: English
• Published: Wiley 2018
• Subjects: Arctic; Arctic ground squirrel; Urocitellus parryii
• Online Access: http://dx.doi.org/10.1096/fasebj.2018.32.1_supplement.805.29

Hibernation is a phenomenon brought on by seasonal changes in phenotype. In the arctic ground squirrels (AGS), the effect of these seasonal changes is very evident. In late fall AGS decrease their metabolic demand which is followed by the entry into hibernation in winter. Previously the lab has shown that N 6 ‐cyclohexyladenosine (CHA), an A 1 adenosine receptor agonist, induces hibernation in AGS in a seasonally dependent manner. AGS treated with CHA in winter experience a decrease in the rate of oxygen consumption and temperature as seen during natural hibernation during winter. However, in summer CHA triggers a brief and transient metabolic suppression that does not lead to hibernation onset. CHA induces hibernation at a location within the CNS, but specific sites of action are unknown. Here we utilize cFos expression to identify neuronal cell groups differentially activated in summer and in winter after CHA. AGS implanted with body temperature (T b ) transmitter, were treated with CHA or vehicle (0.5 mg/kg, IP). Metabolic rate was measured via open‐flow respirometry. AGS were perfused with 4% paraformaldehyde and brains were dissected and cryoprotected in 5%, 10%, 15%, 20%, 30% sucrose. We performed free‐floating immunohistochemistry on 40 μm brain slices in four experimental groups: winter CHA, winter control, summer CHA and summer control. We sectioned brains from eight AGS per group for a total of 32 animals and identified active nuclei with cFos immunoreactivity (mouse anti‐cFos 1:20,000, Millipore). Blinded analysis of cFos immunoreactive neurons was done using bright field microscopy and Metamorph software. Statistical analysis was performed on R. CHA produced a hibernation‐like response measured as a decrease in metabolic rate and T b in winter AGS but not in the summer. Two regions showed greater activation following CHA indicated by higher count of cFos+ neurons: the Nucleus Tractus Solitarius (NTS) and the Median Preoptic Nucleus (MnPO). The NTS has been described previously as a site of action for ...