Scientists have long been intrigued by the question of which factors drive seasonal hibernation in mammals. In 1992, a team of Japanese researchers lead by Noriaki Kondo offered the first hint of an explanation. They found that the expression of specific protein complexes in the blood of hibernators was seasonally regulated and decreased significantly before the onset of hibernation. They proposed a seasonally regulated molecular network influenced by the so-called `hibernation specific protein complex', which they suggested could modulate hibernation in mammals. However, it was not clear how the complex regulated hibernation. Following his initial breakthrough, Kondo combined forces with colleagues from several Japanese research institutions to try to identify the complex's function, and in a recent issue of Cellthey describe how they have shown that hibernation specific protein complex is a hormone that carries chemical signals essential for hibernation to the brain.

The team chose to work with a champion hibernator, the Asiatic chipmunk. Inducing torpor in animals (by exposing them to the cold and dark conditions of winter), while stimulating summer levels of activity in other chipmunks (by exposing them to long warm days), the team measured the complex's gene expression levels in the liver and protein levels in the blood of both groups of animals. They observed that chipmunks from both groups had very different protein complex level patterns, which appeared to be correlated with their hibernation state; animals exposed to perpetual summer retained annually fluctuating and seasonally dependent levels of the complex. The team concluded that the hibernation specific protein complex production was endogenously regulated according to the animals precisely ticking circannual clock.

Curious to know where the newly found factor takes effect, the team directed their attention to the chipmunks' brains and analysed hibernation specific protein complex levels in the cerebrospinal fluid. Kondo and his collaborators found that hibernation specific protein complex levels in the blood and the brain were inversely regulated. They found that before hibernation, complex levels were high in the brain but low in the blood. They explained that this could indicate that hibernation specific protein complex becomes activated when it enters the chipmunk's brain. From the similarity of the complex with other hormones that are produced in the liver before transportation to, and activation in, the brain, the team concluded that they have isolated a hormone for hibernation.

Suspecting that hibernation specific protein complex regulates hibernation in the brain, the team tested whether disrupting the hormone with antibodies targeted to the complex may block the process. By doing so, Kondo and his colleagues were able to prevent some of the animals from going into hibernation, while reducing the length of other animals' torpor. Thus, they demonstrated, that the `hibernation hormone' develops its function in the brain.

Of course, the holy grail of hibernation research is to eventually apply the mechanisms to non-hibernators, such as ourselves; hibernation specific protein complex could send us into hibernation too. Perhaps, the dream of sending torpid astronauts to Mars will soon come true.

References

Kondo, N., Sekijima, T., Kondo, J., Takamatsu, N., Tohya K.,Ohtsu, T. (
2006
). Circannual control of hibernation by HP Complex in the brain.
Cell
125
,
161
-172.