SCI ADV: Heavy! Scientists identify key neurons that maintain normal body temperature in mammalian organisms

Researchers don't know exactly what the bidirectional controller of the thermoregulatory center in the preoptic area (POA) looks like
。 Recently, a study entitled "Prostaglandin EP3 receptor-expressing preoptic neurons bidirectionally control body temperature via tonic GABAergic signaling" published in the international journal Science Advances.
Scientists from Nagoya University and other institutions in Japan have found that a special type of neuron called EP3 neurons in the preoptic area of the brain may play a key role in regulating the body temperature of mammals, and this finding is expected to help develop a new technology to artificially regulate the body's body temperature to help treat heat stroke, hypothermia and even obesity
.

The body temperature of humans and many other mammals is regulated at about 37 degrees Celsius (98.
6 degrees Fahrenheit), which helps optimize all regulatory functions, and when the body temperature deviates significantly from the normal range, the body's function is impaired, which can lead to heat stroke, hypothermia, and in the worst case, death
.
However, if the body temperature can be artificially adjusted to the normal range, these conditions can be effectively treated
.
The brain's thermoregulatory center is located in the preoptic area, which is part of the hypothalamus that controls key functions of the body, for example, when the preoptic area receives a signal from a mediator called prostaglandin E (PGE2), which releases a command to raise body temperature to help defend against viruses, bacteria and other pathogenic organisms, PGE2 production can respond
to infection.

However, researchers do not know what kind of neurons in the preoptic region can release instructions to increase or decrease the body's body temperature, in order to identify which kind of neurons, researchers Kazuhiro Nakamura and others studied rats, focusing on the EP3 neurons in the preoptic area, which can express the EP3 receptor of PGE2, and the researchers also investigated its function
to regulate body temperature 。 In this study, the researchers analyzed for the first time how the activity of EP3 neurons in the preoptic area changes with the change of ambient temperature; The rats were exposed to cold (4 degrees), room temperature (24 degrees) and high temperatures (36 degrees) over a two-hour period, and the results showed that exposure to 36 degrees might activate EP3 neurons, while exposure to 4 and 24 degrees did not
.

Scientists identify key neurons
that maintain normal body temperature in mammalian organisms.

Image source: Science Advances (2022).
DOI:10.
1126/sciadv.
add5463

The researchers then observed and analyzed the nerve fibers of EP3 neurons in the preoptic area, aiming to identify where signals from EP3 neurons would be transmitted, and the observation showed that the nerve fibers were distributed in multiple brain regions, especially the dorsomedial hypothalamus region of the hypothalamus, which can activate the sympathetic nervous system of the body; The analysis also showed that the substance used by EP3 neurons to transmit signals to DMH is γ-aminobutyric acid (GABA), a major inhibitor
of neuronal excitation.
In order to further investigate the role of EP3 neurons in temperature regulation, the researchers used a chemogenetic method to artificially manipulate its activity, and found that activating the neuron may help lower body temperature, while inhibiting its activity will increase body temperature
.

The researchers pointed out that EP3 neurons in the preoptic area can control the sympathetic response of the body by releasing GABA to send inhibitory signals to DMH neurons, and play a key role in regulating body temperature.
The possibility is that EP3 neurons in the preoptic area can precisely adjust the signal intensity to fine-tune the body's body temperature
.
For example, in a hot environment, the signal is enhanced to inhibit the output of the sympathetic nerve, resulting in increased blood flow in the skin, thereby promoting the radiation of body heat and preventing heat stroke; However, in cold environments, signals are reduced to activate the body's sympathetic output, which promotes heat production in brown adipose tissue and other organs to prevent hypothermia
.
In addition, PGE2 can exert an action on EP3 neurons to inhibit their activity during infection, resulting in the activation of sympathetic output and the production of a febrile sensation
.

The results of this study may provide new ideas for the development of new technologies for artificial regulation of body temperature, which may also be applied to a wider range of medical fields; Interestingly, the technique may also be used to treat obesity and promote fat burning by maintaining a body temperature slightly above the body's normal level; In addition, the technology is expected to help develop new strategies for people to survive in a hotter global environment, which is currently one of
the biggest problems facing the global population.
In summary, the results of this study suggest that GABAergic heterogeneity signals from POAEP3R neurons may be the basic determinants
of body temperature and fever that maintain body thermohome.
(Biovalley Bioon.
com)

Original source:

YOSHIKO NAKAMURA,TAKAKI YAHIRO,AKIHIRO FUKUSHIMA,et al.
 Prostaglandin EP3 receptor-expressing preoptic neurons bidirectionally control body temperature via tonic GABAergic signaling, Science Advances (2022).
DOI:10.
1126/sciadv.
add5463