- Temperature regulation is one of the core functions of the brain to maintain human cell physiology.
- The thermoregulatory center is located in the hypothalamus of the brain in its preoptic area.
- However, the signaling molecules underlying the activity of these thermoregulatory neurons have not been properly identified.
- Research indicates the response of heat sensitive hypothalamic neurons was abolished in Transient Receptor Potential M2 (TRPM2) knockout mice, suggesting its possible role in the activity of the heat sensitive neurons.
Role of Hypothalamus in Temperature RegulationCore body temperature is controlled by a hierarchy of neural structures. For instance, when the ambient temperature is high, the heat sensitive neurons of the hypothalamus detect the change and initiate heat loss mechanisms such as sweating and cutaneous vasodilation.
To make all this happen a complex mechanism exits throughout the brain stem and spinal cord and it takes place through the effector areas for regulation of temperature. The preoptic region, in the rostral hypothalamus is the coordinating center and strongly influences each of the lower effector areas. It receives the temperature input from the peripheral body thermo-sensors. In addition, it also detects the local brain temperature (core temperature) acting as a central thermo-sensor.
‘It’s getting hot – time to turn on the internal air conditioner.’
AdvertisementBy integrating central and peripheral inputs, it regulates the temperature by appropriate responses.
How Fever is CausedPyrogens released by bacteria, and other mediators cause fever by inhibiting the rate of firing of hypothalamic warm-sensitive neurons and increasing the firing rate of cold sensitive neurons. As a result, heat loss mechanisms are suppressed and heat production and retention mechanisms are increased.
In the presence of pyrogens, the hypothalamic set point temperatures are elevated, and fever occurs. When pyrogen levels diminish, however, firing rates return to their normal, higher levels in warm-sensitive neurons. Cold sensitive neurons are inhibited. This is followed by return to a lower set point temperature.
Function of TRPM2
- It causes release of cytokines and chemokines from macrophages and an enhanced inflammatory response. Since some of these cytokines such as TNF-α and Interleukins are also pyrogens, fever occurs.
- It has been shown to play a role in insulin secretion.
- If this regulation is disturbedit can lead to metabolic and inflammatory conditions such as obesity, diabetes and gout.
Effect of TRPM2 KnockoutIn TRPM2 knockout mice, basal temperature is normal, but there is a blunted fever response.
The firing rate of heat sensitive neurons is normal at the steady state. However, during fever, there is an inability to upregulate the thermostat to a higher temperature resulting in a decreased heat generating activity and consequently milder fever.
Effects of Remotely Controlling Core Body TemperatureDr Song's research may provide a mechanism to remotely control core body temperature in mice.
It may provide an opportunity to study the effects of altered core body temperature on various processes such as obesity, trauma, metabolism and longevity to name a few.
- TRPM2 - (https:en.wikipedia.org/wiki/TRPM2#References)
- Role of the Preoptic-Anterior Hypothalamus in Thermoregulation and Fever - (http://cid.oxfordjournals.org/content/31/Supplement_5/S157.full)
- Identification of key signaling molecules involved in hypothalamic thermoregulation, Dissertation, Kun Song