Ultrasonic brain pulses put mice into a state of hibernation | Science

It’s a classic sci-fi trope: astronauts on interstellar travel are kept in sleek, chilled pods in a state of suspended animation. Although these pods remain purely fictitious, scientists have continued research to induce a hibernation-like state in humans to reduce damage from medical conditions such as heart attacks and strokes, and to reduce the stress and costs of future long-distance space travel.

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 call it a major technical step towards achieving this feat in humans, while others say it’s a stretch to extrapolate the results to our species.

“It’s an incredible paper,” says Frank van Breukelen, a biologist who studies hibernation at the University of Nevada, Las Vegas and co-author of an editorial accompanying the study. The work builds on a host of recent studies that identify specific populations of neurons. in a region called the preoptic area (POA) of the hypothalamus.These cells act as an on-off switch for “torpor” – a slow, energy-efficient state that animals enter when dangerously cold or unwell fed. , scientists genetically engineered these neurons to respond to light or certain chemicals, and found that they could cause mice to go numb even when they were warm and well-fed. “It’s really not going to happen to 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 certain 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 torpor. To see what effect this had on the animals’ behavior, his team then stuck miniature speaker-like devices on the mice’s heads to focus these waves on the POA.

In response to a series of 3.2 megahertz pulses, the rodents’ core body temperature dropped by about 3°C. The mice cooled off by transferring body heat to their tails — a classic sign of torpor, Bruekelen notes — and their heart rate and metabolism slowed. By automatically delivering additional pulses of ultrasound when the animals’ body temperature began to rise, the researchers were able to keep the mice in this torpid state for up to 24 hours. When they silenced the mini-speakers, the mice returned to normal, apparently with no ill effects.

Chen’s team then repeated the experiment on 12 rats – which do not naturally writhe in response to cold or lack of food – and found a similar effect, although their body temperatures only dropped by 1. °C to 2°C. The researchers say this suggests the technique could work even in animals that don’t usually hibernate.

Breukelen says his confidence in the team’s results is bolstered by the fact that when the researchers directed the ultrasound to other regions of the brain, the mice did not appear to enter a torpid state. This suggests that the animals’ reduced metabolism was indeed caused by the specific stimulation of POA neurons, and not simply by the “jamming” of brain function. “I don’t think anyone wants therapy that is just turning off the brain, and the consequences be damned,” he says. It is also encouraged that the researchers recreated the same effect in rats. Although humans do not naturally hibernate, this ability is found in species of nearly every mammalian lineage, from the Madagascar fat-tailed dwarf lemur to the Arctic ground squirrel. Perhaps humans, like rats, also possess a hidden ability to enter something akin to hibernation, he says.

Others are not convinced. Shaun Morrison of Oregon Health & Science University doubts that scientists have actually observed torpor in mice. The 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 temperature in response. Even if the effect is real, he’s skeptical of using ultrasound to put astronauts in suspended animation anytime soon. People’s brains are much larger than mice’s, and the POA is buried deeper, Morrison notes, making it much harder to target with the mini-speakers employed by Chen and his colleagues. “This ultrasound technique is very unlikely to work in humans the way it does in mice.”

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