- 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.
Hypothalamus in Temperature Regulation
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.
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
integrating central and peripheral
it regulates the
temperature by appropriate responses.
How Fever is Caused
Pyrogens released by
and other mediators cause fever by inhibiting
the rate of firing of hypothalamic warm-sensitive neurons
the firing rate of cold sensitive neurons. As a result, heat loss mechanisms
are suppressed and heat production and retention mechanisms are increased.
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
- 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 Knockout
TRPM2 knockout mice, basal temperature is normal, but there is a blunted fever response
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
Effects of Remotely Controlling Core Body
Song's research may provide a mechanism
to remotely control core body temperature in mice
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