Ultrasonic brain stimulation induces hibernation-like state in mice

A groundbreaking study published in the journal Nature Metabolism has presented a non-invasive and safe method to induce torpor in mice and rats. Led by Hong Chen, an assistant professor at Washington University in St. Louis, an interdisciplinary team successfully stimulated the preoptic area of ​​the hypothalamus in the brain with ultrasound, causing a decrease in body temperature and metabolic rate. This torpor-like state, seen in some mammals and birds as a survival mechanism, conserves energy and warmth in difficult environmental conditions. The results obtained open up promising prospects for applications in various fields, from space flight to healthcare.

Chen and her team developed a portable ultrasound transducer that targeted neurons in the preoptic region of the hypothalamus, which are responsible for regulating body temperature and metabolism. When stimulated, the mice experienced a drop in temperature of about 3 degrees Celsius within about an hour. In addition, animal metabolism has shifted from using both carbohydrates and fats to exclusively using fat, which is a key characteristic of torpor. Heart rate decreased by about 47% while maintaining room temperature.

To achieve stable and prolonged ultrasound-induced hypothermia and hypometabolism, the team developed an automatic feedback controller that adjusted the ultrasound output accordingly. This innovative approach successfully maintained a mouse’s body temperature at 32.95 degrees Celsius for approximately 24 hours, which is the critical temperature for natural torpor in mice. After turning off the ultrasound, the body temperature quickly returned to normal.

Further research has focused on unraveling the underlying mechanisms of ultrasound-induced hypothermia and hypometabolism. The team found that ultrasound activated the TRPM2 ion channel in neurons in the hypothalamic preoptic region, which was confirmed by genetic sequencing. Experimental data showed that TRPM2 served as an ultrasound-sensitive ion channel and played a critical role in the induction of torpor.

Interestingly, the researchers also applied their ultrasonic stimulation to rats, which do not naturally go into torpor or hibernation. In response, the rats showed a decrease in skin temperature, especially in the area of ​​brown adipose tissue, and a decrease in core body temperature by about 1 degree Celsius, which resembled natural torpor.

The interdisciplinary team involved in this pioneering study includes Jonathan R. Brestoff, MD, and Alexei W. Kravitz, both from the School of Medicine, and Jianmin Cui from the McKelvey School of Engineering, all at Washington University in St. Louis. Michael R. Brujas of the University of Washington also contributed to the study.

Chen expressed the potential impact of ultrasound-induced hypothermia and hypometabolism, stating, “UIH can address the long-sought goal of achieving non-invasive and safe induction of torpor that has been pursued by the scientific community since at least the 1960s.” Ultrasonic stimulation, with its unique ability to accurately and non-invasively reach deep regions of the brain, holds promise in both animals and humans, marking significant advances in our understanding of energy conservation and biological states.