Final Report Summary - THERMOREG (Peripheral and Central Mechanisms of Temperature Detection and Core Body Thermoregulation)
(i) Using a number of different techniques and methodologies ranging from genetics to proteomics and biochemistry, as well as cellular assays and behavior experiments we identified a pathway that can counteract heat-induced pain. While there is no immediate therapeutic value that can be derived from our study it – nevertheless – has stimulated more research to identify the precise analgesic mechanism and to assess whether a new analgesic target can be derived from this research direction.
(ii) In a separate line of research we investigated cell populations and mechanisms that are important for intrinsic (deep brain) temperature detection and that believed to mediate body temperature homeostasis close to a stable value of 37° Celsius. Albeit temperature sensitivity has been attributed to a small brain region in the hypothalamus that is concerned with thermoregulation, precise cell populations and their mechanisms of action have remained elusive. As part of ThermoReg we have identified such a hypothalamic cell population and characterized a molecular mechanism that would putatively allow these cells to respond to intrinsic temperature changes important for maintaining body temperature homeostasis.
En passant, we discovered a way to induce pronounced and reversible hypothermia in a mouse model system. The novel aspect of this centrally-induced hypothermic state is that the organism is “primed” for a low body temperature and physiological responses –that usually maintain body temperature close to 37° Celsius – are suspended. This raises the possibility to experimentally study potentially beneficial effects of centrally-induced hypothermia (e.g. as a means to prevent tissue damage after a heart attack or stroke) using this novel model system that may have advantages compared to externally “enforced” hypothermia that is conventionally used.