Prolonged body temperature tuning in mice using radio frequency generating electromagnetic resonant circuit-system

Rational In endothermic animals, body temperature (BT) is an evolutionary conserved and well characterized physical parameter that guarantees physiological functioning state. It results from the sum of bioenergetic processes of the body weighted by behavioral strategies, heat loss, and thermolytic processes. However, the intrinsic impact of temperature and temperature changes on the biology is far less understood. To date, the modification of the environmental temperature has constituted the main lever to evaluate the impact of thermic changes in small animal. However, studying intrinsic effect of temperature remains impossible using conventional laboratory equipment, mainly because hypothalamus instructed with information grabbed from the environmental temperature finely regulates and maintain body temperature around 37°C. Numerous pharmacological treatments have been used to block these thermoregulatory mechanisms, but confer high toxicity while dysregulating the central nervous responses and can potentially have confounding direct effects on studied peripheral tissues. Alternatively, physical methods using energy irradiation were reported, but they remain expensive and usually involve animal immobilization. We aimed at designing a simple and affordable device to adjust and maintain body temperature on the long course in conscious and free-moving animals. Method We developed an electromagnetic LC resonant circuit (ELM circuit) producing a radio frequency signal (64 kHz) inside a copper coil refrigerated with a water circuit. This setting is powered by a simple a 0-48V AC generator, allowing the use of a domestic electrical network. This setting can accommodate metal-free 3D-printed circular cages, where adult mice, previously implanted with thermometric ID transponders, are monitored remotely for intraperitoneal temperature over time. Results The BT of mice placed in the ELM circuit could be regulated in a reproducible fashion. Healthy mice increased their BT from 37 to 39.8±1°C, upon power supply ranging from 0 to 48V, respectively. In septic mice developing hypothermia (33±1 °C), BT could be either normalized to normothermia (37°C, 24V), or increased to fever-range hyperthermia (40°C, 48V) as a function of radiofrequency energy. BT tuning was accurate and stable for at least 12h. Blood count after 6 or 12 hours showed no modifications between groups, cardiomyocyte displayed heat shock response within the first hour in mice exposed to the maximal dose (BT=41°C). MALDI TOF imaging on brain microsections revealed modifications of the brain proteome, as suggested by differential PKC-theta, and prolactin 7B1 load in heated mice, as compared to controls. Conclusion Precise body temperature tuning is achievable in small animals, and could be of high interest to understand the impact of temperature in (patho)physiology.