Ultrasound of brain pulses puts mice in a kind of hibernation | Science

It’s a classic sci-fi trope: astronauts on an interstellar journey are kept in a state of suspended animation in tight, refrigerated pods. While such pods remain purely fictional, scientists have been researching inducing a hibernation-like state in humans to reduce the damage caused by medical conditions such as heart attacks and strokes, and reduce the stress and expense of future long-distance space travel .

This is according to a study published today in Nature Metabolism, scientists report that they can induce a similar condition in mice by targeting part of their brains with ultrasonic pulses. Some experts call it a major technical step toward achieving this feat in humans, while others say it’s a stretch to extrapolate the results to our species.

“It’s a great paper,” said Frank van Breukelen, a biologist who studies hibernation at the University of Nevada, Las Vegas and co-authored an editorial accompanying the study. The work builds on a series of recent studies that localize specific populations of neurons. in a region called the preoptic area (POA) of the hypothalamus. These cells act as an on-off switch for “sedation” – a slow, energy-saving state the animals enter when they are dangerously cold or malnourished. In previous studies, scientists genetically engineered these neurons to respond to light or certain chemicals, and found that they could cause mice to go into a limp state even when warm and well-fed. However, such invasive techniques cannot be easily are translated to humans, Breukelen notes, “That’s really not going to happen in humans.”

The new ultrasound study, led by bioengineer Hong Chen and her team at Washington University in St. Louis, did not require genetic engineering. Chen knew from previous research that some neurons have specialized pores called TRPM2 ion channels that change shape in response to ultrasound waves, including the subset of POA cells that control mouse anesthesia. To see what effect that had on the animals’ behavior, her team then taped miniature, speaker-like devices to mice’s heads to direct these waves at the POA.

In response to a series of 3.2 megahertz pulses, the rodents’ body temperature dropped by about 3°C. The mice cooled down by transferring body heat to their tails — a classic sign of torpor, Bruekelen notes — and their heart rates and metabolisms slowed. By automatically delivering extra ultrasound pulses when the animals’ body temperatures started to rise again, the researchers were able to keep the mice in this limp state for up to 24 hours. When they silenced the minispeakers, the mice returned to normal, apparently without ill effects.

Chen’s team then repeated the experiment in 12 rats—who don’t naturally fall asleep in response to cold or food scarcity – and found a similar effect, even though their body temperature only dropped by 1°C to 2°C. The researchers say this suggests the technique could work even in animals that don’t normally hibernate.

Breukelen says his confidence in the team’s results is bolstered by the fact that when the researchers focused the ultrasound on other brain regions, the mice didn’t appear to enter a sleepy state. That suggests that the animals’ reduced metabolism was indeed caused by specifically stimulating the neurons in the POA, and not simply by “distorting” brain function. “I don’t think anyone wants a therapy based on simply turning off the brain, and the consequences are damned,” he says. He’s also encouraged that the researchers mimicked the same effect in rats. While humans don’t naturally hibernate, the ability is found in species from nearly every mammalian lineage, from Madagascar’s fat-tailed pygmy lemur to the Arctic ground squirrel. Perhaps, like the rats, humans also have a hidden ability to enter something akin to hibernation, he says.

Others are not convinced. Shaun Morrison of Oregon Health & Science University doubts whether the scientists actually observed anesthesia in the mice. Ultrasound stimulation warms the brain, he says, so it’s possible the researchers actually activated temperature-sensitive neurons in that region, causing the animals to lower their body temperatures in response. Even if the effect is real, he’s skeptical that we’ll soon be using ultrasonic waves to put astronauts in suspended animation. Human brains are much larger than mouse brains, and the POA is buried more deeply, Morrison notes, making it much harder to target the minispeakers Chen and her colleagues employed. “It is very unlikely that this ultrasound technique works in humans as it does in mice.”

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