A multidisciplinary team led by associate teacher Hong Chen at Washington University in St. Louis has established a novel, noninvasive technique to cause a torpor-like state in mammals by targeting the central nerve system with ultrasound. The technique, which includes promoting the hypothalamus preoptic area in the brain, was revealed to successfully reduce body temperature level and metabolic rate in mice, causing a state of torpor, which is a natural system used by some animals to make it through extreme conditions. Credit: Image courtesy Chen lab, Washington University in St. Louis
Scientists at Washington University in St. Louis have established a method to induce a torpor-like state in mammals utilizing ultrasound stimulation of the brain, according to a study in Nature Metabolism. The noninvasive method could possibly be used in circumstances like area flights or for clients with severe health conditions to conserve energy and heat.
Some mammals and birds have a clever way to preserve energy and heat by entering into torpor, during which their body temperature and metabolic rate drop to enable them to make it through potentially deadly conditions in the environment, such as severe cold or absence of food. While a comparable condition was proposed for researchers making flights to area in the 1960s or for patients with lethal health conditions, safely inducing such a state remains elusive.
Hong Chen, an associate teacher at Washington University in St. Louis, and a multidisciplinary group induced a torpor-like state in mice by utilizing ultrasound to stimulate the hypothalamus preoptic location in the brain, which helps to regulate body temperature and metabolism. In addition to the mouse, which naturally enters into torpor, Chen and her team caused torpor in a rat, which does not. Their findings, published on May 25 in the journal Nature Metabolism, show the very first noninvasive and safe method to induce a torpor-like state by targeting the main anxious system.
A multidisciplinary group led by associate teacher Hong Chen at Washington University in St. Louis has actually established an unique, noninvasive technique to induce a torpor-like state in mammals by targeting the central anxious system with ultrasound. Hong Chen, an associate teacher at Washington University in St. Louis, and a multidisciplinary group induced a torpor-like state in mice by utilizing ultrasound to stimulate the hypothalamus preoptic location in the brain, which helps to manage body temperature and metabolism. Chen, associate teacher of biomedical engineering at the McKelvey School of Engineering and of radiation oncology at the School of Medicine, and her group, including Yaoheng (Mack) Yang, a postdoctoral research partner, produced a wearable ultrasound transducer to stimulate the neurons in the hypothalamus preoptic location.” We developed an automated closed-loop feedback controller to achieve long-duration and steady ultrasound-induced hypothermia and hypometabolism by managing of the ultrasound output,” Chen stated. Chen and her group also desired to find the particle that permitted these nerve cells to trigger with ultrasound.
By Washington University in St. Louis
May 28, 2023
Chens team utilized ultrasound to securely, noninvasively induce a torpor-like state in mice, rats. Credit: Video courtesy Chen lab, Washington University in St. Louis
Chen, associate teacher of biomedical engineering at the McKelvey School of Engineering and of radiation oncology at the School of Medicine, and her group, including Yaoheng (Mack) Yang, a postdoctoral research study partner, developed a wearable ultrasound transducer to promote the nerve cells in the hypothalamus preoptic location. When promoted, the mice showed a drop in body temperature level of about 3 degrees Celsius for about one hour. In addition, the mices metabolic process revealed a modification from utilizing both carbohydrates and fat for energy to only fat, a crucial feature of torpor, and their heart rates fell by about 47%, all while at room temperature.
The team also discovered that as the acoustic pressure and period of the ultrasound increased, so did the depth of the lower body temperature and slower metabolism, understood as ultrasound-induced hypothermia and hypometabolism (UIH).
” We established an automated closed-loop feedback controller to achieve long-duration and steady ultrasound-induced hypothermia and hypometabolism by managing of the ultrasound output,” Chen said. “The closed-loop feedback controller set the desired body temperature level to be lower than 34 C, which was formerly reported as crucial 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 typical temperature after ultrasound was off.”
To learn how ultrasound-induced hypothermia and hypometabolism is activated, the group studied the characteristics of the activity of neurons in the hypothalamus preoptic area in reaction to ultrasound. They observed a constant increase in neuronal activity in reaction to each ultrasound pulse, which aligned with the modifications in body temperature in the mice.
” These findings revealed that UIH was evoked by ultrasound activation of hypothalamus preoptic area nerve cells,” Yang said. “Our finding that transcranial stimulation of the hypothalamus preoptic location was enough to cause UIH revealed the important function of this area in orchestrating a torpor-like state in mice.”
Chen and her group also wished to find the particle that enabled these nerve cells to trigger with ultrasound. Through hereditary sequencing, they found that ultrasound activated the TRPM2 ion channel in the hypothalamus preoptic location nerve cells. In a variety of experiments, they revealed that TRPM2 is an ultrasound-sensitive ion channel and added to the induction of UIH.
In the rat, which does not naturally enter into torpor or hibernation, the group delivered ultrasound to the hypothalamus preoptic location and discovered a reduction in skin temperature, particularly in the brown fat region, along with about a 1 degree C drop in core body temperature, resembling natural torpor.
This multidisciplinary group 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 likewise includes Michael R. Bruchas, a teacher of anesthesiology and of pharmacology at the University of Washington.
” UIH has the possible to address the long popular objective of accomplishing noninvasive and safe induction of the torpor-like state, which has been pursued by the clinical community at least because the 1960s,” Chen stated. “Ultrasound stimulation has an 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, r01eb030102, and r01eb027223). JRB is supported by NIH (DP5 OD028125) and Burroughs Wellcome Fund (CAMS # 1019648).