title: Neuronal UCP1 expression suggests a mechanism for local thermogenesis during hibernation.
abstract: Hibernating mammals possess a unique ability to reduce their body temperature to ambient levels, which can be as low as -2.9 °C, by active down-regulation of metabolism. Despite such a depressed physiologic phenotype, hibernators still maintain activity in their nervous systems, as evidenced by their continued sensitivity to auditory, tactile, and thermal stimulation. The molecular mechanisms that underlie this adaptation remain unknown. We report, using differential transcriptomics alongside immunohistologic and biochemical analyses, that neurons from thirteen-lined ground squirrels (Ictidomys tridecemlineatus) express mitochondrial uncoupling protein 1 (UCP1). The expression changes seasonally, with higher expression during hibernation compared with the summer active state. Functional and pharmacologic analyses show that squirrel UCP1 acts as the typical thermogenic protein in vitro. Accordingly, we found that mitochondria isolated from torpid squirrel brain show a high level of palmitate-induced uncoupling. Furthermore, torpid squirrels during the hibernation season keep their brain temperature significantly elevated above ambient temperature and that of the rest of the body, including brown adipose tissue. Together, our findings suggest that UCP1 contributes to local thermogenesis in the squirrel brain, and thus supports nervous tissue function at low body temperature during hibernation.
authors.affiliation: Department of Cellular and Molecular Physiology, Program in Cellular Neuroscience, Neurodegeneration and Repair, and.
authors.forename: Willem J
authors.initials: WJ
authors.lastname: Laursen
authors.affiliation: Department of Cellular and Molecular Physiology, Program in Cellular Neuroscience, Neurodegeneration and Repair, and.
authors.forename: Marco
authors.initials: M
authors.lastname: Mastrotto
authors.affiliation: Department of Cellular and Molecular Physiology, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06510;
authors.forename: Dominik
authors.initials: D
authors.lastname: Pesta
authors.affiliation: Department of Cellular and Molecular Physiology.
authors.forename: Owen H
authors.initials: OH
authors.lastname: Funk
authors.affiliation: Department of Cellular and Molecular Physiology, Program in Cellular Neuroscience, Neurodegeneration and Repair, and.
authors.forename: Jena B
authors.initials: JB
authors.lastname: Goodman
authors.affiliation: Department of Biology, University of Wisconsin, Oshkosh, WI 54901; and.
authors.forename: Dana K
authors.initials: DK
authors.lastname: Merriman
authors.affiliation: Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Ingolia
authors.affiliation: Department of Cellular and Molecular Physiology, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06510;
authors.forename: Gerald I
authors.initials: GI
authors.lastname: Shulman
authors.affiliation: Department of Cellular and Molecular Physiology, elena.gracheva@yale.edu sviatoslav.bagriantsev@yale.edu.
authors.forename: Sviatoslav N
authors.initials: SN
authors.lastname: Bagriantsev
authors.affiliation: Department of Cellular and Molecular Physiology, Program in Cellular Neuroscience, Neurodegeneration and Repair, and elena.gracheva@yale.edu sviatoslav.bagriantsev@yale.edu.
authors.forename: Elena O
authors.initials: EO
authors.lastname: Gracheva
mesh_terms: D000818:Animals; D006605:Hibernation; D007473:Ion Channels / Q000378:metabolism / Q000502:physiology*; D008928:Mitochondria / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000378:metabolism / Q000502:physiology*; D009474:Neurons / Q000378:metabolism*; D012589:Sciuridae; D022722:Thermogenesis; D000071256:Uncoupling Protein 1
chemical_list: D007473:Ion Channels; D024101:Mitochondrial Proteins; D000071256:Uncoupling Protein 1
keywords: UCP1; hibernation; thermogenesis; thirteen-lined ground squirrel; uncoupling protein