Humans and many other mammals maintain their body temperature at about 37°C (98.6°F), which is ideal for all regulatory processes. Their functions are compromised when their body temperatures deviate noticeably from the normal range, which can lead to heat stroke, hypothermia or, in the worst cases, death. However, if body temperature can be artificially brought into the normal range, these problems can be corrected.

The preoptic area of ​​the hypothalamus, which regulates the body’s essential processes, is where the brain’s temperature control center is located. For example, the preoptic area sends a signal to the body to raise its temperature to fight off viruses, germs, and other disease-causing organisms when it receives signals from the mediator prostaglandin E (PGE2), which is produced in response to infections.

However, it is still unclear which neurons in the preoptic area give the command to increase or decrease body temperature.

A research group at Nagoya University in Japan has identified critical neurons that maintain mammalian body temperature at 37°C. In their study, they reported that a group of neurons called EP3 neurons in the preoptic region of the brain play a key role in regulating mammalian body temperature.

In the rat study, scientists mainly focused on EP3 neurons in the preoptic region, which express EP3 receptors of PGE2, and investigated its function in regulating body temperature.

Scientists first investigated how variations in ambient temperature affect the firing of EP3 neurons in the preoptic area. Rats like a temperature of about 28 °C for their living environment. The mice were exposed to cold (4°C), room (24°C) and warm (36°C) conditions for two hours. The findings showed that exposure to 4°C and 24°C did not activate EP3 neurons, but exposure to 36°C did.

To determine where the signals from EP3 neurons are transmitted, the scientists then looked at the nerve fibers of EP3 neurons in the preoptic area. The study found that nerve fibers are scattered throughout the brain, especially in the dorsomedial hypothalamus (DMH), which is responsible for activating the sympathetic nervous system. Gamma-aminobutyric acid (GABA), a potent inhibitor of neuronal excitation, is the molecule that EP3 neurons use to signal transmission to DMH, according to their research.

Scientists experimentally altered the activity of EP3 neurons using a chemogenetic method to better understand the function of these neurons in temperature regulation. They found that raising body temperature resulted from suppressing the activity of the neurons, while lowering it resulted from activating them.

Together, the results of this study showed that EP3 neurons in the preoptic area are essential for controlling body temperature, as they release GABA to transmit inhibitory signals to DMH neurons, which regulate sympathetic responses.

Professor Kazuhiro Nakamura at Nagoya University said: “Probably EP3 neurons in the preoptic area can precisely regulate signal strength to fine-tune body temperature.”

“In a hot environment, for example, signals are amplified to suppress sympathetic outputs, resulting in increased blood flow in the skin to facilitate body heat radiation to prevent heat stroke. However, in a cold environment, signals are reduced to activate sympathetic outputs, which promote heat production in brown adipose tissue and other organs to prevent hypothermia. In addition, at the time of infection, PGE2 acts on EP3 neurons to suppress their activity, triggering sympathetic outputs to develop fever.

The results of this study could lead to the creation of a technology that artificially modifies body temperature and has potential applications in many medical specialties. Interestingly, this technology may help treat obesity by maintaining a slightly elevated body temperature that stimulates fat burning.

prof. Nakamura said: “In addition, this technology could lead to new strategies for human survival in warmer global environments, which are becoming a serious global problem.”

Magazine reference:

  1. Yoshiko Nakamura, Takaki Yahiro et al. Prostaglandin EP3 receptor-expressing preoptic neurons bidirectionally regulate body temperature via tonic GABAergic signaling. Scientific progress. DOI: 10.1126/sciadv.add5463