Project description:Mammalian hibernators display phenotypes similar to physiological conditions in non-hibernating species under conditions of calorie restriction and fasting, hypoxia, hypothermia, ischemia-reperfusion, and sleep. However, whether or how similarities are also reflected on molecular and genetic levels is unclear. We identified molecular signatures of torpor and arousal in hibernation using a new custom-designed cDNA microarray for the arctic ground squirrel (Urocitellus parryii,) and compared them to molecular signatures of selected phenotypes in mouse. Our results show that differential gene expression related to metabolism during torpor is closely related to that during calorie restriction and hypoxia. PPARM-NM-1 is crucial for metabolic remodeling in hibernation. Genes related to the sleep-wake cycle and temperature response genes induced by hypothermia follow the same expression changes as in torpor-arousal cycle. Increased fatty acid metabolism might contribute to the protection against ischemia-reperfusion injury during hibernation. Further, by comparing with thousands of pharmacological signatures, we identified drugs that may induce similar expression patterns in human cell lines as during hibernation. Arctic ground squirrels sampled during winter hibernation were compared with the animals sampled during summer. Liver was hybridized on a custom 9,600 probes nylon membrane microarray platform. Four squirrels in early torpor, five in late torpor, four in early arousal, four in late arousal, and seven in summer active were studied in experiments.
Project description:Mammalian hibernators survive prolonged periods of cold and resource scarcity by temporarily modulating normal physiological functions, but the mechanisms underlying these adaptations are poorly understood. The hibernation cycle of thirteen-lined ground squirrels lasts for 5–7 months and comprises weeks of hypometabolic, hypothermic torpor interspersed with 24–48-hour periods of an active-like interbout arousal (IBA) state. We show that ground squirrels, who endure the entire hibernation season without food, have negligible hunger drive during IBAs. We further demonstrate that squirrels exhibit reversible inhibition of the hypothalamic feeding center, such that hypothalamic arcuate nucleus neurons have reduced sensitivity to the orexigenic and anorexigenic effects of ghrelin and leptin, respectively. However, hypothalamic infusion of thyroid hormone during an IBA is sufficient to rescue hibernation anorexia. Our results reveal that thyroid hormone deficiency underlies hibernation anorexia and demonstrate the functional flexibility of the hypothalamic feeding center.
2024-04-03 | GSE242381 | GEO
Project description:RAD sequencing of Idaho ground squirrels