• Thu. Jun 8th, 2023

Ultrasound brain pulses put mice in a hibernation-like state | Science


May 25, 2023

It’s a classic science fiction trope: Astronauts on an interstellar journey are kept in sleek, refrigerated pods in a state of suspended animation. Although such pods remain purely fictional, scientists have pursued research into inducing a hibernation-like state in humans to lessen the damage caused by medical conditions such as heart attacks and stroke, and to reduce the stress and costs of future long-distance space sojourns.

In a study published today in Nature Metabolism, scientists report that they can trigger a similar state in mice by targeting part of their brain with pulses of ultrasound. Some experts are calling it a major technical step toward achieving this feat in humans, whereas others say it’s a stretch to extrapolate the results to our species.  

“It’s an amazing paper,” says 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 flurry of recent studies that pinpoint specific populations of neurons in a region called the preoptic area (POA) of the hypothalamus. These cells act like an on-off switch for “torpor”—a sluggish, energy-saving state the animals enter when they’re dangerously cold or malnourished. In previous studies, scientists genetically engineered these neurons to respond to light or certain chemicals, and found they could cause mice to enter a torpid state even when they were warm and well-fed. Such invasive techniques can’t be easily translated to people, however, Breukelen notes. “That’s really not going to happen in people.”

The new ultrasound study, led by bioengineer Hong Chen and her team at Washington University in St. Louis required no genetic engineering. Chen knew from previous research that some neurons have specialized pores called TRPM2 ion channels that change shape in response to ultrasonic waves, including the subset of POA cells that controls mouse torpor. To see what effect that had on the animals’ behavior, her team next glued miniature, speakerlike devices on the heads of mice to focus these waves on the POA.

In response to a series of 3.2-megahertz pulses, the rodents’ core body temperatures dropped by about 3°C. The mice cooled off by shifting body heat into their tails—a classic sign of torpor, Bruekelen notes—and their heart rates and metabolisms slowed. By automatically delivering additional pulses of ultrasound when the animals’ body temperatures began to climb back up, the researchers could keep the mice in this torpid state for up to 24 hours. When they silenced the minispeakers, the mice returned to normal, apparently with no ill consequences.

Chen’s team then repeated the experiment in 12 rats—which don’t naturally go into torpor in response to cold or food scarcity—and found a similar effect, although their body temperatures only dropped by 1°C to 2°C. The researchers say this suggests the technique might work even in animals that don’t ordinarily hibernate.

Breukelen says his confidence in the team’s results is strengthened by the fact that when the researchers directed the ultrasound to other brain regions, the mice didn’t appear to enter a torpid state. That suggests the animals’ reduced metabolism was indeed caused by stimulating specifically the neurons in the POA, and not simply by “scrambling” brain functioning. “I don’t think anyone wants a therapy that relies on simply turning off the brain, and consequences be damned,” he says. He’s also encouraged that the researchers re-created the same effect in rats. Although humans don’t naturally hibernate, the ability is found in species from nearly every mammalian lineage, from Madagascar’s fat-tailed dwarf lemur to the arctic ground squirrel. Perhaps humans, like the rats, also possess a hidden capacity for entering something akin to hibernation, he says.

Others aren’t convinced. Shaun Morrison at Oregon Health & Science University doubts the scientists really observed torpor in the mice. Ultrasound stimulation warms up the brain, he says, so it’s possible the researchers were in fact activating 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 be using ultrasound to put astronauts into suspended animation anytime soon. People’s brains are much bigger than the brains of mice and the POA is buried deeper, Morrison notes, making it much more difficult to target with the minispeakers Chen and her colleagues employed. “This ultrasound technique is very unlikely to work in humans in the way it does in mice.”

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