[Investigation of mechanisms of mammalian hibernation and its possible application in medical treatment].

Mammalian hibernation has been reported to increase resistance to various harmful events such as low body temperature, severe ischemia, bacterial infection, irradiation, and muscle disuse, and to prolong the lifespan of the mammal. Therefore, hibernation mechanisms are thought to play a critical role in maintaining healthy organisms. Although the application of this physiological phenomenon to medical fields has strongly been desired, it has been prevented by a poor understanding of the hibernation mechanism. In order to clarify how mammalian hibernation is controlled in organisms, we have looked for a physiological signal of hibernation and found marked changes in cardiac calcium regulation associated with a circannual hibernation. Focusing on these changes, we initially discovered a molecular marker of hibernation, hibernation-specific proteins (HP), of which production in the liver and the blood content are controlled by an endogenous circannual rhythm responsible for hibernation. Our recent studies on HP regulation have revealed that circannual signals for the timing of hibernation are transmitted through the neuroendocrine system and that HP are actively transported into the cerebrospinal fluid (CSF) prior to the onset of hibernation. This suggested that hibernation is controlled by HP in the brain and its regulation system. Based on these results, the future medical application of these results is discussed.