A groundbreaking study published in Nature Metabolism has unveiled a noninvasive and safe method to induce a torpor-like state in mice and rats. Led by Hong Chen, an associate professor at Washington University in St. Louis, the multidisciplinary team successfully stimulated the hypothalamus preoptic area in the brain using ultrasound, triggering a drop in body temperature and metabolic rate. This torpor-like state, observed in certain mammals and birds as a survival mechanism, conserves energy and heat in challenging environmental conditions. The findings offer promising prospects for applications in various fields, from space travel to healthcare.
Chen and her team designed a wearable ultrasound transducer that targeted the neurons in the hypothalamus preoptic area, responsible for regulating body temperature and metabolism. When stimulated, mice exhibited a temperature drop of approximately 3 degrees Celsius for about an hour. Furthermore, the animals’ metabolism shifted from using both carbohydrates and fat to solely relying on fat, a key characteristic of torpor. Heart rates decreased by approximately 47%, all while maintaining room temperature.
To achieve stable and long-lasting ultrasound-induced hypothermia and hypometabolism, the team developed an automatic closed-loop feedback controller that adjusted the ultrasound output accordingly. This innovative approach successfully maintained the mouse body temperature at 32.95 degrees Celsius for around 24 hours, aligning with the critical temperature for natural torpor in mice. Once the ultrasound was deactivated, the body temperature promptly returned to normal.
Further investigations focused on unraveling the underlying mechanisms of ultrasound-induced hypothermia and hypometabolism. The team discovered that ultrasound activated the TRPM2 ion channel in the hypothalamus preoptic area neurons, as confirmed through genetic sequencing. Experimental evidence demonstrated that TRPM2 served as an ultrasound-sensitive ion channel and played a crucial role in inducing the torpor-like state.
Interestingly, the researchers also applied their ultrasound stimulation to rats, which do not naturally enter torpor or hibernation. In response, the rats exhibited a decrease in skin temperature, particularly in the brown adipose tissue region, and a core body temperature drop of approximately 1 degree Celsius, resembling natural torpor.
The multidisciplinary team involved in this groundbreaking research includes Jonathan R. Brestoff, MD, PhD, and Alexxai V. 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. Bruchas from the University of Washington also contributed to the study.
Chen expressed the potential impact of ultrasound-induced hypothermia and hypometabolism, stating, “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.” Ultrasound stimulation, with its unique ability to reach deep brain regions precisely and noninvasively, holds promise for both animal and human applications, marking a significant advancement in our understanding of energy conservation and biological states.