Mices sent into hibernation

go into hibernation
D. Balasubramanian
U.S scientists have coaxed laboratory mice to go into a hibernation-like state by making them inhale air laced with the gas hydrogen sulphide.
ANIMALS SUCH as the polar bear cope with the severe Arctic winter by shutting down their activities for months on end.
During this period of hibernation, they cut down their breathing and metabolism to the basic minimum, and drop their body temperature from the usual 37 Celsius to 15 or below. On the other side of the coin are some desert animals, which too go on a similar shut-off mode as the summer heat scorches up to beyond 45 Celsius. This hot weather torpor behaviour is called aestivation.
Drop in metabolism
Either form of inactivity — hibernation or aestivation — is marked by drops in metabolism, breathing rate and body temperature. As the weather turns more agreeable, these animals return to normal biological activity.
Laboratory mice, born and bred in animal houses neither hibernate nor aestivate. They live in air-conditioned comfort round the year, with a steady supply of food and water. Now, scientists at the Fred Hutchinson Cancer Center at Seattle, Washington, USA have coaxed these laboratory mice to go into a hibernation- like state for about six hours! They did this by making these mice inhale air laced with about 80 parts per million (ppm) of the gas hydrogen sulphide or H{-2}S. Yes, the same gas that smells like rotten eggs!
Reporting in the the journal Science, Eric Blackstone, Mike Morrison and Mark Roth show that when exposed to hydrogen sulphide gas, the metabolic rate of these mice dropped by 90 per cent, their breathing rate by over 50 per cent, and their body temperature dropped from the usual 37 Celsius to 15 degrees.
After six hours of exposure, when the mice were returned to the usual room air and temperature, they returned to normal. The researchers conclude that hydrogen sulphide induces a suspended animation-like state in mice.
Medical benefits
These results are of interest since on-demand induction of such a lowered metabolic state may have some medical benefits. It could be used for improving the preservation of organs used for transplantation. It could also be useful in reducing physiological damage resulting from trauma, and improving outcomes after some forms of surgery.
What is it about hydrogen sulphide that evokes this hibernation-like response? This compound is known to be a potent, specific and reversible inhibitor of a key step in metabolic energy production. Biochemical molecules in cells and tissues transact their energy business in the form of a high-energy molecule called ATP.
ATP is thus often referred to as the energy currency of cells. Hydrogen sulphide appears to modulate the catalytic action of a key enzyme called cytochrome c oxidase, which produces ATP.
This inhibition of ATP production is believed to reduce metabolic activity. Hydrogen sulphide does this reversibly, so that when it is removed from the system, normalcy returns.
Transmitter of signals
Dr. Rui Wang of the University of Saskatchewan in Canada has been working on the biological effects of hydrogen sulphide, and considers this compound to be the third simple gas that acts as a transmitter of signals in cells.
The other two signal transmitter gases are nitric oxide or NO and carbon monoxide or CO. Both have well defined functions at physiologically relevant concentrations.
They help in relaxing blood vessels and modulating the central nervous system in specific ways. Wang catalogues (in his paper in FASEB Journal, 16, 1792, 2002) the role of hydrogen sulphide in similar terms. Importantly, all these three gases are also generated within cells through biochemical reactions.
They all have specific molecular targets on which they act and evoke responses. For example, NO and CO activate membrane channels through which calcium is allowed to pass.
Hydrogen sulphide is also produced within cells by certain enzymes, and appears to modulate ATP channels. Some have already started wondering whether humans too can go into hibernation through smelling hydrogen sulphide.
Poison at high doses
Let me point out right away that this gas is a poison at high doses and can even kill an organism. For mice, the optimal dose was worked out to be 80 ppm.
The Seattle researchers had also satisfied themselves that after six hours of the gas, when the mice returned to normal state, they had suffered no ill effects.
What the safe and effective dose in humans will be is yet to be worked out. Controlled and rigorous trials on volunteers need to be done before these results can be translated to humans.
And, one friend asked whether yogis and monks who experience suspended animation-like states might be inducing this gas in their body cells through some method or the other.
It is too premature to jump into conclusions; let us meditate first on the mice.
dbala@lvpei.org