Central nervous system regulation of mammalian hibernation: Implications for metabolic suppression and ischemia tolerance

Kelly L. Drew, C. Loren Buck, Brian M. Barnes, Sherri L. Christian, Brian T. Rasley, Michael B. Harris

Research output: Contribution to journalReview articlepeer-review

131 Scopus citations

Abstract

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 H2S 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.

Original languageEnglish (US)
Pages (from-to)1713-1726
Number of pages14
JournalJournal of Neurochemistry
Volume102
Issue number6
DOIs
StatePublished - Sep 2007
Externally publishedYes

Keywords

  • Metabolic arrest
  • Metabolic suppression
  • Suspended animation

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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