create a method to induce torpor with ultrasound

by time news

2023-05-25 17:00:05

We all know the case of bear hibernation: with the arrival of winter, they lie in their caves, asleep; your metabolism slows down, body temperature drops to the minimum necessary to keep the main vital signs active, thus drastically reducing the energy consumption that the body needs. Heart rate also slows, breathing sluggish, and brain activity slows to subsistence levels. When they wake up again, although somewhat thinner, they are perfectly healthy. The same practice is carried out by marmots, raccoons, snakes and swallows, among others.

Researchers have been wondering for decades if a similar state could be induced in humans to ‘stop’ life-threatening diseases (for example, when metabolism is reduced, cells need less oxygen, so in diseases such as stroke or heart failure hibernation may be neuroprotective) or to realize the dream of space travel beyond the Moon (in fact, the first human visit to Mars, scheduled for the next decade, would be greatly simplified with this system). At the moment, there is no method, but science is taking small steps. The last one is to induce this state in mice -which naturally hibernate- and in rats -which do not- by using ultrasound. The results have just been published in the journal ‘Nature Metabolism’.

Specifically, the team led by Hong Chen, a biomedical engineer at Washington University in St. Louis, induced a state of lethargy that they have named “torpor” in rats and mice using an ultrasound system that stimulates the preoptic area. of the hypothalamus in the brain, which helps regulate body temperature and metabolism.

A method of success

When stimulated, the mice showed a drop in body temperature of about 3 degrees Celsius for about an hour. In addition, the mice’s metabolism showed a switch from using carbohydrates and fat for energy to just fat, a key feature of torpor, and their heart rates dropped by about 47%, all while at room temperature.

The team also found that as acoustic pressure and ultrasound duration increased, so did the depth of lower body temperature and slower metabolism, known as ultrasound-induced hypothermia and hypometabolism (UIH).

“We developed a closed-loop automatic feedback controller to achieve stable and long-lasting ultrasound-induced hypothermia and hypometabolism by controlling the ultrasound output,” Chen explains. “The closed-loop feedback controller set the target body temperature to less than 34°C, which was previously reported to be critical for natural torpor in mice. This feedback-controlled UIH maintained the mouse’s body temperature at 32.95°C for approximately 24 hours and recovered to normal temperature after the ultrasound was turned off.”

To learn how ultrasound-induced hypothermia and hypometabolism are activated, the team studied the dynamics of activity of neurons in the preoptic area of ​​the hypothalamus in response to ultrasound. They observed a steady increase in neural activity in response to each ultrasound pulse, which aligned with changes in the mice’s body temperatures.

“These findings revealed that the UIH was caused by ultrasound activation of neurons in the preoptic area of ​​the hypothalamus,” says the researcher. “Our finding that transcranial stimulation of the preoptic area of ​​the hypothalamus was sufficient to induce UIH revealed the pivotal role of this area in orchestrating a torpid state in mice.”

Chen and his team also wanted to find the molecule that would allow these neurons to fire with ultrasound. Through genetic sequencing, they found that ultrasound activated the TRPM2 ion channel in neurons in the preoptic area of ​​the hypothalamus. In a variety of experiments, they demonstrated that TRPM2 is an ultrasound-sensitive ion channel and contributed to the induction of UIH.

Testing the system in rats, animals that do not hibernate

In the rat, which does not naturally go into torpor or hibernation, the team tested the same method and found a decrease in skin temperature, particularly in the region of brown adipose tissue, as well as a drop of approximately 1ºC in temperature. body, resembling natural lethargy.

“UIH has the potential to address the long-sought goal of achieving safe, non-invasive induction of torpor, which has been pursued by the scientific community since at least the 1960s,” Chen notes. “Ultrasound stimulation possesses a unique ability to non-invasively reach deep regions of the brain with high spatial and temporal precision in animal and human brains.”

The scientific community, divided

Undoubtedly, achieving an efficient mechanism to induce hibernation is a very juicy goal due to its multiple applications. “This is a significant advance, since it is the first to use a non-invasive technology,” says Matteo Cerri, associate professor of Physiology in the Department of Biomedical and Neuromotor Sciences at the University of Bologna (Italy) for SMC Spain. “The main limitation is the very modest effect of the technology in rats (although present). Therefore, there is still work to be done. We may be heading towards a composite system, which can fuse ultrasound stimulation with drugs to achieve significant hypometabolism in humans.”

For his part, Vladyslav Vyazovskiy, Professor of Sleep Physiology at the University of Oxford (United Kingdom) points out to the same platform that, although it is likely that a state of hibernation will be induced in humans in the future, “the neurophysiological mechanisms and underlying molecules can be very different from those of other animals.” ‘For example, daily torpor can be induced in mice by acute fasting, and this does not occur in humans, to our knowledge. Seasonal hibernators begin preparing for hibernation many weeks before hibernation occurs, and this can happen even without any external input. Humans are less seasonal and therefore the mechanisms and meaning of hibernation in humans can be very different,” he says.

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