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Scientists discover how to use ultrasound to send mice into torpor [1]
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Date: 2023-05-31
A few days ago, the New York Times relayed this story: “Ultrasound Pulses to Brain Send Mice into a Hibernation-Like State”:
Researchers reported in the journal Nature Metabolism on Thursday that they’ve been able to send mice into a torpor-like state by targeting a specific part of the brain with short bursts of ultrasound.
That portion of the brain is called the preoptic area (POA). The POA is situated within the hypothalamus (a cubic centimeter known as the master gland, as it controls the pituitary gland as well as maintains other life-supporting functions of the body such as sleep, thirst, and temperature).
The POA itself is concerned with thermoregulation, which makes it an attractive target for scientists interested in inducing torpor, a state of stilled or suspended metabolism. (Fans of Vampire: the Masquerade and other enthusiasts of fantasy lore might recognize torpor as the state where the fantastic creature goes into an unnatural state of sleep, where they’re almost impossible to stir.) Britannica.com defines torpor more definitively:
torpor, a state of lowered body temperature and metabolic activity assumed by many animals in response to adverse environmental conditions, especially cold and heat. The torpid state may last overnight, as in temperate-zone hummingbirds and some insects and reptiles; or it may last for months, in the case of true hibernation and the winter torpor of many cold-blooded vertebrates.
As Yaoheng Yang and colleagues, the authors of the Nature Metabolism study, themselves say,
The concept of inducing torpor-like hypothermia and hypometabolism by artificial means was initially proposed in 1960 as a biomedical solution to reduce energy consumption during long-term human spaceflight.
Like other concepts originating from midcentury, this idea has driven research to the point where what was science fiction is nearing science fact. We’ve been chasing this dream for years.
The key to generating this state of lowered metabolism is the use of ultrasound, technology that utilizes sound above 20,000 Hz. This is often used in devices crafted to create images for use in the medical field as well as in many other applications, such as testing structures for flaws.
The researchers relate that
Ultrasound is the only available energy form that can noninvasively penetrate the skull and focus on any location within the brain with millimeter precision and without ionizing radiation. These capabilities, along with its safety, portability and low cost, have made ultrasound a promising technology for neuromodulation in small animals, non-human primates and humans, although its mechanism remains elusive.
Here we have ultrasound being beamed into a very particular spot in the mouse brain to create a state of hibernation, what the scientists call UIH [ultrasound-induced hypothermia and hypometabolism]. They also created this effect in rats, an unnatural state for such an animal.
Hover over picture for description as described in the study.
As the New York Times reported:
Dr. Chen and her colleagues constructed tiny ultrasound mouse caps. The devices trained six bursts, each consisting of 10 seconds of ultrasound, on the selected area of the rodent’s brain. … The mice, the researchers noticed, stopped moving. Measurements of their body temperature, heart rate and metabolism showed a pronounced dip. The mice stayed in this state for about an hour after the ultrasound bursts, and then returned to normal.
ISI, inter-stimulus interval; PD, pulse duration; PRF, pulse repetition frequency.
The scientists were able to precisely control the depth and duration of this ultrasound-induced hypothermia, which they state in their report as “the key to successfully engineering the torpor-like state.”
They then isolated the protein in the POA neurons, TRPM2, that is responsible for this effect by tracking Ca2+ (calcium ion) flux. “In summary, the POA neurons and TRPM2 ion channel are likely to be activated by the mechanical and thermal effects of ultrasound,” the authors state, though they caution that “[t]he biophysical mechanisms for ultrasound activation of POA neurons and the TRPM2 ion channel remain to be discovered.”
Also found to be involved in the process were “the dorsomedial hypothalamus as a downstream brain region and brown adipose tissue as an effector tissue” in the regulation of this induced hypothermic state. Interestingly, brown adipose tissue, which specializes in expending energy through non-shivering thermogenesis, has a role in the interplay of melatonin, a neurochemical involved in circadian rhythm.
Infrared thermal images in top row; corresponding photos underneath.
The behavior of the heart radically changes.
This study comes on the heels of another that was published last November in Nature Communications whereby Shuai Zhang and associates found that “deep brain stimulation of warm-sensitive neurones in the medial preoptic nucleus produces tolerable hypothermia.” Their method creates a non-shivering thermogenesis but requires the insertion of an electrode. The method described by Yang and colleagues, on the other hand, can induce this state with non-invasive ultrasound.
Yang and his team sum their findings with this bit of optimism:
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[1] Url:
https://www.dailykos.com/stories/2023/5/31/2172339/-Scientists-discover-how-to-use-ultrasound-to-send-mice-into-torpor
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