Ultrasound can trigger a hibernation-like state in mice and rats

Zapping part of the brain with focused ultrasound can put mice in a hibernation-like state called torpor for at least 24 hours. The same approach can also induce the state in rats, which, unlike mice, don’t naturally enter torpor.

“That has huge implications,” says Hong Chen at Washington University in St. Louis, Missouri. “The thinking is that, if we show that in animals that don’t normally enter the torpor state we can still induce a similar phenomenon, maybe we can scale up the technology to larger animals.”

If this can be done in people, too, it could have medical uses among other things. For instance, inducing torpor in people who have had strokes could buy them time and help limit the damage, says Chen.

Many warm-blooded animals lower their body temperature and slow down their metabolism to save energy, entering torpor. Some bats and birds go into torpor at night. Others, such as mice, enter it only when food runs low. Hibernation involves extended periods of torpor interrupted by occasional returns to normal body temperature.

In 2020, two teams independently discovered that stimulating part of the hypothalamus in the brains of mice can induce torpor. However, they used complex methods, including genetic engineering, to activate this “brain switch”.

Chen wondered if ultrasound could be used instead. Her team has been developing a method called focused ultrasound for treating brain diseases.

Chen’s team found that a 10-second pulse of ultrasound focused on the brain switch area in mice led to their body temperature falling by around 3°C (5.4°F). The mice recovered completely after 2 hours, but by delivering repeated pulses whenever their body temperature started to rise, it was possible to keep the animals in this state for 24 hours with no sign of ill effects.

It might be possible to maintain this state for much longer, says Chen, but her team hasn’t yet tried to do this.

While the technique also works in rats, their body temperature only fell by around 1.3°C (2.3°F).

“Although modest, this is important because rats are non-hibernators and, in this, closer to humans,” says Matteo Cerri at the University of Bologna in Italy, whose team has induced torpor in rats and pigs by chemically inhibiting a part of the brainstem.

Lowering body temperature with ultrasound could be useful for medical purposes, but interplanetary travel may require more robust ways to suppress metabolism, says Cerri.

Exactly how the focused ultrasound induces torpor isn’t clear, says Takeshi Sakurai at the University of Tsukuba in Japan, whose team was one of the two that discovered the hypothalamus switch.

It might be triggering this brain switch, says Sakurai. “However, there are also other groups of neurons in the nearby region that play a role in thermoregulation, making it more likely that they are also involved.”

Chen thinks that a combination of the local heating and physical movement induced by the focused ultrasound opens ion channels on neurons, activating them. But this remains to be established.

Any potential human uses are still far off, she says. “Safety is a big concern.” Focused ultrasound that is too intense or that is maintained for too long can damage the brain, and her team had to do a lot of experiments to work out a safe dose in a mouse.

But it is entirely feasible to develop a helmet that could deliver focused ultrasound pulses to the equivalent part of the human brain, she says.