Ultrasound Induction of Torpor-Like State in Mammals Achieved by Scientists at Washington University

Monday - May 29 2023, 22:00 UTC - 1 year ago

Scientists at Washington University in St. Louis have developed a method to induce torpor-like states in mammals using noninvasive ultrasound stimulation of the brain. The technique could be used for applications in space and for patients with extreme health conditions to preserve energy and heat. The technique was tested in mice and rats, with successful results. The results, published in Nature Metabolism on May 25, demonstrate the first safe and noninvasive way to induce a torpor-like state in mammals via targeting the central nervous system.

Scientists at Washington University in St. Louis have developed a method to induce a torpor-like state in mammals using ultrasound stimulation of the brain, according to a study in Nature Metabolism. The noninvasive technique could potentially be used in scenarios like space flights or for patients with severe health conditions to conserve energy and heat.

Some mammals and birds have a clever way to preserve energy and heat by going into torpor, during which their body temperature and metabolic rate drop to allow them to survive potentially fatal conditions in the environment, such as extreme cold or lack of food. While a similar condition was proposed for scientists making flights to space in the 1960s or for patients with life-threatening health conditions, safely inducing such a state remains elusive.

Hong Chen, an associate professor at Washington University in St. Louis, and a multidisciplinary team induced a torpor-like state in mice by using ultrasound to stimulate the hypothalamus preoptic area in the brain, which helps to regulate body temperature and metabolism. In addition to the mouse, which naturally goes into torpor, Chen and her team induced torpor in a rat, which does not. Their findings, published on May 25 in the journal Nature Metabolism, show the first noninvasive and safe method to induce a torpor-like state by targeting the central nervous system.

Chen’s team used ultrasound to safely, noninvasively induce a torpor-like state in mice, rats. Credit: Video courtesy Chen laboratory, Washington University in St. Louis .

Chen, associate professor of biomedical engineering at the McKelvey School of Engineering and of radiation oncology at the School of Medicine, and her team, including Yaoheng (Mack) Yang, a postdoctoral research associate, created a wearable ultrasound transducer to stimulate the neurons in the hypothalamus preoptic area. When stimulated, the mice showed a drop in body temperature of about 3 degrees Celsius for about one hour. In addition, the mice’s metabolism showed a change from using both carbohydrates and fat for energy to only fat, a key feature of torpor, and their heart rates fell by about 47%, all while at room temperature.

The team also found that as the acoustic pressure and duration of the ultrasound increased, so did the depth of the lower body temperature and slower metabolism, 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," Chen said. "The closed-loop feedback controller set the desired body temperature to be lower than 34 °C, which was 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 ultrasound was off." .

To learn how ultrasound-induced hypothermia and hypometabolism is activated, the team studied the dynamics of the activity of neurons in the hypothalamus preoptic area in response to ultrasound. They observed a consensually sustained increase of the firing activity of the neurons in response to continuous ultrasound, which activates the chill-flight response.