Final Report Summary - THERMOREG (Peripheral and Central Mechanisms of Temperature Detection and Core Body Thermoregulation)
At the outset, ThermoReg was principally conceived to delineate mechanisms of temperature (heat) detection that are important in two very diverse aspects of thermal biology: in pain sensation and thermoregulation. Using rodents as a model ThermoReg made essentially 2 important contributions:
(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.
(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.