Induced hibernation-like state in mice could be key for long-term space travel

When stimulated in mice, it showed a nearly 3-degree Celsius drop in body temperature for an hour. Furthermore, the mice's metabolism for energy consumption switched from using both carbohydrates and fat to only relying on fat — one of the critical characteristics of achieving torpor. During this state, their heart rates also decreased by 47 percent. 

Scientifically speaking, the increased acoustic pressure and duration of the ultrasound resulted in lower body temperature and slower metabolism, which is known as ultrasound-induced hypothermia and hypometabolism (UIH).

“We developed an automatic closed-loop feedback controller to achieve long-duration and stable ultrasound-induced hypothermia and hypometabolism by controlling of the ultrasound output,” explained Hong Chen, an associate professor at the university, in an official statement. 

“The closed-loop feedback controller set the desired body temperature to be lower than 34 C, previously reported as critical for natural torpor in mice. This feedback-controlled UIH kept the mouse body temperature at 32.95 C for about 24 hours and recovered to normal temperature after the ultrasound was off,” Chen added.

However, the researchers were unsure how ultrasound-induced hypothermia and hypometabolism get evoked in the brain region. To figure this out, the team monitored neuron activity in the brain region about the ultrasound pulse. Neuronal activity increased in response to each ultrasound pulse, which aligned to the mice's body temperature drop.

Through genetic sequencing, they found that ultrasound activated the "TRPM2 ion channel" in the hypothalamus preoptic area neurons. 

The researchers repeated the experiments with rats and noted similar results, albeit with a slightly less drop in body temperature (1 to 2 degrees Celsius). 

Some experts believe it is a major milestone toward ultimately achieving this state in humans, and the procedure could be especially beneficial in future medical and space travel applications.

The findings have been published in the journal Nature Metabolism.  

Study abstract:

Torpor is an energy-conserving state in which animals dramatically decrease their metabolic rate and body temperature to survive harsh environmental conditions. Here, we report the noninvasive, precise and safe induction of a torpor-like hypothermic and hypometabolic state in rodents by remote transcranial ultrasound stimulation at the hypothalamus preoptic area (POA). We achieve a long-lasting (>24 h) torpor-like state in mice via closed-loop feedback control of ultrasound stimulation with automated detection of body temperature. Ultrasound-induced hypothermia and hypometabolism (UIH) is triggered by activation of POA neurons, involves the dorsomedial hypothalamus as a downstream brain region and subsequent inhibition of thermogenic brown adipose tissue. Single-nucleus RNA-sequencing of POA neurons reveals TRPM2 as an ultrasound-sensitive ion channel, the knockdown of which suppresses UIH. We also demonstrate that UIH is feasible in a non-torpid animal, the rat. Our findings establish UIH as a promising technology for the noninvasive and safe induction of a torpor-like state.