Central nervous system regulation of mammalian hibernation: implications for metabolic suppression and ischemia tolerance.
Torpor during hibernation defines the nadir of mammalian metabolism where whole animal rates of metabolism are decreased to as low as 2% of basal metabolic rate. This capacity to decrease profoundly the metabolic demand of organs and tissues has the potential to translate into novel therapies for the treatment of ischemia associated with stroke, cardiac arrest or trauma where delivery of oxygen and nutrients fails to meet demand. If metabolic demand could be arrested in a regulated way, cell and tissue injury could be attenuated. Metabolic suppression achieved during hibernation is regulated, in part, by the central nervous system through indirect and possibly direct means. In this study, we review recent evidence for mechanisms of central nervous system control of torpor in hibernating rodents including evidence of a permissive, hibernation protein complex, a role for A1 adenosine receptors, mu opiate receptors, glutamate and thyrotropin-releasing hormone. Central sites for regulation of torpor include the hippocampus, hypothalamus and nuclei of the autonomic nervous system. In addition, we discuss evidence that hibernation phenotypes can be translated to non-hibernating species by H(2)S and 3-iodothyronamine with the caveat that the hypothermia, bradycardia, and metabolic suppression induced by these compounds may or may not be identical to mechanisms employed in true hibernation.
Drew
Kelly L
KL
Institute of Arctic Biology, Alaska Basic Neuroscience Program, University of Alaska Fairbanks, Fairbanks, Alaska, USADepartment of Chemistry and Biochemistry, Alaska Basic Neuroscience Program, University of Alaska Fairbanks, Fairbanks, Alaska, USADepartment of Biological Sciences, University of Alaska Anchorage, Anchorage, Alaska, USA.
Buck
C Loren
CL
Institute of Arctic Biology, Alaska Basic Neuroscience Program, University of Alaska Fairbanks, Fairbanks, Alaska, USADepartment of Chemistry and Biochemistry, Alaska Basic Neuroscience Program, University of Alaska Fairbanks, Fairbanks, Alaska, USADepartment of Biological Sciences, University of Alaska Anchorage, Anchorage, Alaska, USA.
Barnes
Brian M
BM
Institute of Arctic Biology, Alaska Basic Neuroscience Program, University of Alaska Fairbanks, Fairbanks, Alaska, USADepartment of Chemistry and Biochemistry, Alaska Basic Neuroscience Program, University of Alaska Fairbanks, Fairbanks, Alaska, USADepartment of Biological Sciences, University of Alaska Anchorage, Anchorage, Alaska, USA.
Christian
Sherri L
SL
Institute of Arctic Biology, Alaska Basic Neuroscience Program, University of Alaska Fairbanks, Fairbanks, Alaska, USADepartment of Chemistry and Biochemistry, Alaska Basic Neuroscience Program, University of Alaska Fairbanks, Fairbanks, Alaska, USADepartment of Biological Sciences, University of Alaska Anchorage, Anchorage, Alaska, USA.
Rasley
Brian T
BT
Institute of Arctic Biology, Alaska Basic Neuroscience Program, University of Alaska Fairbanks, Fairbanks, Alaska, USADepartment of Chemistry and Biochemistry, Alaska Basic Neuroscience Program, University of Alaska Fairbanks, Fairbanks, Alaska, USADepartment of Biological Sciences, University of Alaska Anchorage, Anchorage, Alaska, USA.
Harris
Michael B
MB
Institute of Arctic Biology, Alaska Basic Neuroscience Program, University of Alaska Fairbanks, Fairbanks, Alaska, USADepartment of Chemistry and Biochemistry, Alaska Basic Neuroscience Program, University of Alaska Fairbanks, Fairbanks, Alaska, USADepartment of Biological Sciences, University of Alaska Anchorage, Anchorage, Alaska, USA.
D000818:Animals; D017776:Autonomic Pathways / Q000033:anatomy & histology / Q000502:physiology; D001481:Basal Metabolism / Q000187:drug effects / Q000502:physiology*; D001921:Brain / Q000033:anatomy & histology / Q000502:physiology; D002545:Brain Ischemia / Q000378:metabolism* / Q000503:physiopathology / Q000517:prevention & control; D002490:Central Nervous System / Q000502:physiology*; D004734:Energy Metabolism / Q000502:physiology*; D006605:Hibernation / Q000187:drug effects / Q000502:physiology*; D008322:Mammals / Q000502:physiology*; D011956:Receptors, Cell Surface / Q000378:metabolism
D011956:Receptors, Cell Surface