Les scientifiques induisent un état semblable à l’hibernation en utilisant la stimulation cérébrale par ultrasons

Selon une étude réalisée en métabolisme naturel. Cette technologie non invasive peut être utilisée dans des scénarios tels que les vols spatiaux ou pour les patients souffrant de graves problèmes de santé afin de conserver l’énergie et la chaleur.

Certains mammifères et oiseaux ont un moyen intelligent de conserver l’énergie et la chaleur en entrant dans un état d’hibernation, dans lequel leur température corporelle et leur taux métabolique chutent pour leur permettre de survivre à des conditions mortelles dans l’environnement, comme le froid extrême ou le manque de nourriture. Alors qu’une condition similaire a été proposée pour les scientifiques effectuant des voyages spatiaux dans les années 1960 ou pour les patients souffrant de problèmes de santé potentiellement mortels, l’induction en toute sécurité d’une telle condition reste encore loin.

Hong Chen, professeur agrégé à l’Université de Washington à Saint-Louis, et une équipe multidisciplinaire ont induit un état d’hibernation chez la souris en utilisant des ultrasons pour stimuler une région préopératoire du cerveau, qui aide à réguler la température corporelle et le métabolisme. En plus de la souris, qui hiberne naturellement, Chen et son équipe ont induit l’hibernation chez les souris, ce qui n’est pas le cas. Leurs conclusions, publiées le 25 mai dans la revue Nature métabolisme naturela démontré la première méthode non invasive et sûre pour induire un état de type hibernation en ciblant le système nerveux central.

L’équipe de Chen a utilisé les ultrasons pour induire de manière sûre et non invasive un état de type hibernation chez les souris et les rats. Crédit : Vidéo avec l’aimable autorisation de Chen Lab, Université de Washington à St. Louis

Chen, professeure adjointe de génie biomédical à la McKelvey School of Engineering and Radiation Oncology du College of Medicine, et son équipe, dont Yaoheng (Mack) Yang, associée de recherche postdoctorale, ont créé un transducteur à ultrasons portable pour stimuler les cellules nerveuses dans le hypothalamus. Lors de la stimulation, les souris ont montré une diminution de la température corporelle d’environ 3 degrés[{ » attribute= » »>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).