Sound waves can trigger torpor-like state in mice and rats

The researchers speculate it could save lives and help us explore deep space — if it works on people. But big challenges remain.

Sending pulses of ultrasound waves into the brain appears to trigger an energy-conserving state called “torpor” in animals — and if it does the same in people, it could revolutionize everything from healthcare to space exploration. But figuring out where and how to test it safely will be a big challenge.

Torpor 101: When food is scarce or the weather outside is frightful, some animals will go into “torpor,” a state of deep sleep during which their body temperature drops, their heart rate and breathing slow down, and metabolism slows. It usually lasts for less than a day, and its purpose is to allow the animal to conserve energy.

Humans are not one of the animals naturally capable of torpor, but if we can figure out some way to trigger it in people, we have an ever-growing list of potential applications.

Inducing torpor in people who’ve just experienced a stroke or cardiac arrest, for example, could potentially prevent brain damage. We might be able to use torpor to extend the human lifespan, and it could potentially allow astronauts to survive long missions to deep space with less food and a lower risk of radiation damage, too.

Ultrasound stimulation put the rodents into a state similar to torpor, an energy-conserving deep sleep.

The challenge: Thanks to decades of research, scientists now know that torpor is linked to certain brain neurons, and several groups have induced torpor in mice and rats by genetically engineering them so that those neurons could be specifically triggered by light or chemicals.

Like humans, rats aren’t naturally capable of torpor, so this suggests inducing it in us might be possible, too, but genetically engineering people to put them into a state of deep sleep is too complicated and risky — we’d need a less invasive option.

What’s new? By stimulating the brains of mice and rats with ultrasound waves, researchers at the Washington University in St. Louis (WUSTL) were able to put the rodents into a torpor-like state they call “ultrasound-induced hypothermia and hypometabolism” (UIH).

In this state, both animals demonstrated a drop in body temperature, and the mice also experienced slowed heart rates and changes in metabolism indicative of torpor. Unlike previous studies, this technique didn’t require any genetic modification.

The researchers were able to maintain the torpor-like state in the mice for 24 hours.

How it works: For their study, the researchers created a tiny ultrasound device for the rodents to wear on their heads. They then triggered it to deliver six pulses of ultrasound waves to the preoptic area of the hypothalamus (POA), a part of the brain linked to torpor.

This lowered the body temperature of the mice by 3 degrees Celsius — about the same drop seen in mice during natural, fasting-induced torpor — for one hour. The animals’ heart rates fell by 47%, and they started metabolizing only fat rather than a mix of fat and carbohydrates, a change witnessed during natural torpor.

By delivering more pulses when the mice’s body temperatures started to increase, the researchers were able to maintain the torpor-like state in the animals for 24 hours. When the ultrasound stimulation stopped, the mice returned to their normal state, with seemingly no ill effects.

To understand how the ultrasound pulses were able to trigger these changes, the researchers studied the brain activity of the mice during the experiment and saw that the stimulation activated neurons in the POA.

Through genetic sequencing, they further learned that a protein called TRPM2 is key to this activation — when they reduced its presence in the brain, the mice weren’t as susceptible to the ultrasound stimulation. This information could be useful when trying to translate the approach to other species.

The cold water: The impact of the ultrasound stimulation on the rats seemingly wasn’t as profound — the rodents’ core body temperatures dropped by 1-2°C, but the researchers didn’t report any change in heart rate or metabolism.

It’s also possible that the change in body temperature for both species wasn’t a sign of torpor at all. As neurologist Shaun Morrison, who wasn’t involved in the WUSTL study, told Science Magazine, ultrasound stimulation heats up the brain, and the body’s drop in temperature might have simply been a natural response to that warming.

The big picture: The discovery of a noninvasive way to induce a torpor-like state in animals is exciting, but much more research is needed before we could trial the technique in humans. If it does work in people, though, it could have a huge impact both here on Earth and in space. 

“UIH has the potential to address the long sought-after goal of achieving noninvasive and safe induction of the torpor-like state, which has been pursued by the scientific community at least since the 1960s,” said lead researcher Hong Chen.

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