Circannual Control of Hibernation by HP Complex in the Brain

Seasonal hibernation in mammals is under a unique adaptation system that protects organisms from various harmful events, such as lowering of body temperature (Tb), during hibernation. However, the precise factors controlling hibernation remain unknown. We have previously demonstrated a decrease in hibernation-specific protein (HP) complex in the blood of chipmunks during hibernation. Here, HP is identified as a candidate hormone for hibernation. In chipmunks kept in constant cold and darkness, HP is regulated by an individual free-running circannual rhythm that correlates with hibernation. The level of HP complex in the brain increases coincident with the onset of hibernation. Such HP regulation proceeds independently of Tb changes in constant warmth, and Tb decreases only when brain HP is increased in the cold. Blocking brain HP activity using an antibody decreases the duration of hibernation. We suggest that HP, a target of endogenously generated circannual rhythm, carries hormonal signals essential for hibernation to the brain.

[1]  N. Kondo.  Comparison between effects of caffeine and ryanodine on electromechanical coupling in myocardium of hibernating chipmunks: role of internal Ca stores , 1988, British journal of pharmacology.

[2]  E. Gwinner,et al.  Circadian and circannual programmes in avian migration , 1996, The Journal of experimental biology.

[3]  J. Aschoff.  Annual Rhythms in Man , 1981 .

[4]  U. Kishore,et al.  Modular organization of proteins containing C1q-like globular domain. , 1999, Immunopharmacology.

[5]  N. Kondo.  Excitation-contraction coupling in the myocardium of hibernating chipmunks , 1986, Experientia.

[6]  Alan D. Lopez,et al.  Mild therapeutic hypothermia to improve the neurologic outcome after cardiac arrest. , 2002, The New England journal of medicine.

[7]  T. Shiba,et al.  Hibernation-associated gene regulation of plasma proteins with a collagen-like domain in mammalian hibernators , 1993, Molecular and cellular biology.

[8]  P. Iaizzo,et al.  Muscle strength in overwintering bears , 2001, Nature.

[9]  P. W. Hochachka.  Defense strategies against hypoxia and hypothermia. , 1986, Science.

[10]  K. Frerichs,et al.  Hibernation in Ground Squirrels Induces State and Species-Specific Tolerance to Hypoxia and Aglycemia: An In Vitro Study in Hippocampal Slices , 1998, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[11]  R. L. Ruben,et al.  Effect of 7,12-dimethylbenz(a)anthracene on the integument of the hibernating and nonhibernating 13-lined ground squirrel. , 1982, Comparative biochemistry and physiology. C: Comparative pharmacology.

[12]  F. Goodwin,et al.  Seasonal affective disorder. A description of the syndrome and preliminary findings with light therapy. , 1984, Archives of general psychiatry.

[13]  Carolyn L. Smith,et al.  Primary structure of human corticosteroid binding globulin, deduced from hepatic and pulmonary cDNAs, exhibits homology with serine protease inhibitors. , 1987, Proceedings of the National Academy of Sciences of the United States of America.

[14]  T. Gustafson,et al.  Complete amino acid sequence of human thyroxine-binding globulin deduced from cloned DNA: close homology to the serine antiproteases. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[15]  D. Houlihan,et al.  Advances in Comparative and Environmental Physiology , 1991, Advances in Comparative and Environmental Physiology.

[16]  J. Szmydynger-Chodobska,et al.  Choroid plexus: Target for polypeptides and site of their synthesis , 2001, Microscopy research and technique.

[17]  J. Kondo,et al.  Identification of novel blood proteins specific for mammalian hibernation. , 1992, The Journal of biological chemistry.

[18]  Dieter Häussinger,et al.  Advances in Comparative and Environmental Physiology , 1993, Advances in Comparative and Environmental Physiology.

[19]  N. Otmakhov,et al.  Functional stability of the brain slices of ground squirrels, Citellus undulatus, kept in conditions of prolonged deep periodic hypothermia: Electrophysiological criteria , 1990, Neuroscience.

[20]  J. R. Bamburg,et al.  Extracts from the brains of hibernating and alert ground squirrels: effects on cells in culture. , 1982, Proceedings of the National Academy of Sciences of the United States of America.

[21]  V. Sharapov.  Influence of animal hibernation on the development of mycoses , 1984, Mycopathologia.

[22]  L. Wang.  Mammalian Hibernation: An Escape from the Cold , 1988 .

[23]  U. Lahaie,et al.  Seasonal Affective Disorder , 1986, British Journal of Psychiatry.

[24]  N. Kondo,et al.  Calcium source for excitation-contraction coupling in myocardium of nonhibernating and hibernating chipmunks. , 1984, Science.

[25]  S. Martin,et al.  Central role for differential gene expression in mammalian hibernation. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[26]  H. Lodish,et al.  Proteolytic cleavage product of 30-kDa adipocyte complement-related protein increases fatty acid oxidation in muscle and causes weight loss in mice. , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[27]  L. Gerwick,et al.  The acute phase response and innate immunity of fish. , 2001, Developmental and comparative immunology.

[28]  N. Kondo.  Identification of a pre-hibernating state in myocardium from nonhibernating chipmunks , 1987, Experientia.

[29]  Michael Holzer,et al.  Mild therapeutic hypothermia to improve the neurologic outcome after cardiac arrest , 2002 .

[30]  R. K. Meyer,et al.  HIBERNATION AND THE ENDOCRINES1 , 1939 .

[31]  N. Kondo.  Excitation-contraction coupling in myocardium of nonhibernating and hibernating chipmunks: effects of isoprenaline, a high calcium medium, and ryanodine. , 1986, Circulation research.

[32]  T. Shiba,et al.  Expression of multiple alpha1-antitrypsin-like genes in hibernating species of the squirrel family. , 1997, Gene.

[33]  S. Uchida,et al.  Adiponectin stimulates glucose utilization and fatty-acid oxidation by activating AMP-activated protein kinase , 2002, Nature Medicine.

[34]  C. P. Lyman.  Hibernation and Torpor in Mammals and Birds , 1983 .

[35]  J. Sambrook,et al.  Molecular Cloning: A Laboratory Manual , 2001 .

[36]  T. Shiba,et al.  The tree squirrel HP-25 gene is a pseudogene. , 2001, European journal of biochemistry.