By
A multidisciplinary workforce led by affiliate professor Hong Chen at Washington University in St. Louis has developed a novel, noninvasive methodology to induce a torpor-like state in mammals by focusing on the central nervous system with ultrasound. The approach, which entails stimulating the hypothalamus preoptic space within the mind, was proven to successfully cut back physique temperature and metabolic charge in mice, resulting in a state of torpor, which is a pure mechanism utilized by some animals to outlive excessive situations. Credit: Image courtesy Chen laboratory, Washington University in St. Louis
Scientists at Washington University in St. Louis have developed a technique to induce a torpor-like state in mammals utilizing ultrasound stimulation of the mind, based on a examine in Nature Metabolism. The noninvasive approach might probably be utilized in situations like house flights or for sufferers with extreme well being situations to preserve vitality and warmth.
Some mammals and birds have a intelligent strategy to protect vitality and warmth by going into torpor, throughout which their physique temperature and metabolic charge drop to permit them to outlive probably deadly situations within the atmosphere, similar to excessive chilly or lack of meals. While an analogous situation was proposed for scientists making flights to house within the 1960s or for sufferers with life-threatening well being situations, safely inducing such a state stays elusive.
Hong Chen, an affiliate professor at Washington University in St. Louis, and a multidisciplinary workforce induced a torpor-like state in mice by utilizing ultrasound to stimulate the hypothalamus preoptic space within the mind, which helps to control physique temperature and metabolism. In addition to the mouse, which naturally goes into torpor, Chen and her workforce induced torpor in a rat, which doesn’t. Their findings, printed on May 25 within the journal Nature Metabolism, present the primary noninvasive and secure methodology to induce a torpor-like state by focusing on the central nervous system.
Chen’s workforce used ultrasound to soundly, noninvasively induce a torpor-like state in mice, rats. Credit: Video courtesy Chen laboratory, Washington University in St. Louis
Chen, affiliate professor of biomedical engineering on the McKelvey School of Engineering and of radiation oncology on the School of Medicine, and her workforce, together with Yaoheng (Mack) Yang, a postdoctoral analysis affiliate, created a wearable ultrasound transducer to stimulate the neurons within the hypothalamus preoptic space. When stimulated, the mice confirmed a drop in physique temperature of about three levels 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 consistent increase in neuronal activity in response to each ultrasound pulse, which aligned with the changes in body temperature in the mice.
“These findings revealed that UIH was evoked by ultrasound activation of hypothalamus preoptic area neurons,” Yang said. “Our finding that transcranial stimulation of the hypothalamus preoptic area was sufficient to induce UIH revealed the critical role of this area in orchestrating a torpor-like state in mice.”
Chen and her team also wanted to find the molecule that allowed these neurons to activate with ultrasound. Through genetic sequencing, they found that ultrasound activated the TRPM2 ion channel in the hypothalamus preoptic area neurons. In a variety of experiments, they showed that TRPM2 is an ultrasound-sensitive ion channel and contributed to the induction of UIH.
In the rat, which does not naturally go into torpor or hibernation, the team delivered ultrasound to the hypothalamus preoptic area and found a decrease in skin temperature, particularly in the brown adipose tissue region, as well as about a 1 degree C drop in core body temperature, resembling natural torpor.
This multidisciplinary team consists of Jonathan R. Brestoff, MD, PhD, an assistant professor of pathology and immunology at the School of Medicine; Alexxai V. Kravitz, an associate professor of psychiatry, of anesthesiology and of neuroscience at the School of Medicine, and Jianmin Cui, a professor of biomedical engineering at the McKelvey School of Engineering, all at Washington University in St. Louis. The team also includes Michael R. Bruchas, a professor of anesthesiology and of pharmacology at the University of Washington.
“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,” Chen said. “Ultrasound stimulation possesses a unique capability to noninvasively reach deep brain regions with high spatial and temporal precision in animal and human brains.”
Reference: “Induction of a torpor-like hypothermic and hypometabolic state in rodents by ultrasound” by Yaoheng Yang, Jinyun Yuan, Rachael L. Field, Dezhuang Ye, Zhongtao Hu, Kevin Xu, Lu Xu, Yan Gong, Yimei Yue, Alexxai V. Kravitz, Michael R. Bruchas, Jianmin Cui, Jonathan R. Brestoff and Hong Chen, 25 May 2023, Nature Metabolism.
DOI: 10.1038/s42255-023-00804-z
This work was supported by the National Institutes of Health (R01MH116981, UG3MH126861, R01EB027223, and R01EB030102). JRB is supported by NIH (DP5 OD028125) and Burroughs Wellcome Fund (CAMS #1019648).
