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New study : EP3 neurons in the preoptic area of ​​the brain plays a key role in regulating body temperature in mammals

A group of neurons, called EP3 neurons, in the preoptic area of ​​the brain plays a key role in regulating body temperature in mammals, a research group at Nagoya University in Japan has reported. The finding could pave the way for the development of technology that artificially adjusts body temperature to help treat heat stroke, hypothermia and even obesity. The new study was published in the journal Science Advances.

Body temperature in humans and many other mammals is regulated at approximately 37 °C (98.6 °F), which optimizes all regulatory functions. When their body temperature deviates noticeably from the normal range, their functions are disrupted, which can lead to heatstroke, hypothermia, and in the worst case, death. However, these conditions can be treated if the body temperature can be artificially adjusted to a normal range.

The brain’s temperature regulation center resides in the preoptic area, which is the part of the hypothalamus that controls the body’s vital functions. For example, when the preoptic area receives signals from a mediator called prostaglandin E (PGE2), which is produced in response to infections, the area issues a command to increase body temperature to fight viruses, bacteria, and other disease-causing organisms.

 However, it is still not clear exactly which neurons in the preoptic area release the commands to increase or decrease body temperature. To identify such neurons, Professor Kazuhiro Nakamura, Lecturer Yoshiko Nakamura and their colleagues from Nagoya University, in collaboration with Professor Hiroyuki Hioki from Juntendo University, conducted a study on rats. They focused on EP3 neurons in the preoptic area, which express EP3 PGE2 receptors, and investigated the function of body temperature regulation.

Professor Nakamura and his colleagues first investigated how the activity of EP3 neurons in the preoptic area changes in response to changes in ambient temperature. The comfortable temperature of the environment for rats is around 28 °C. The researchers exposed the rats to cold (4°C), room (24°C) and hot (36°C) temperatures for two hours. The results showed that exposure to 36°C activated EP3 neurons, whereas exposure to 4°C and 24°C did not.

The team then observed the nerve fibers of EP3 neurons in the preoptic area to identify where signals from EP3 neurons are transmitted. The observation revealed that the nerve fibers are distributed to different areas of the brain, especially the dorsomedial hypothalamus (DMH), which activates the sympathetic nervous system. Their analysis also showed that the substance EP3 neurons use to signal to the DMH is gamma-aminobutyric acid (GABA), a major inhibitor of neuronal excitation.

To further investigate the role of EP3 neurons in temperature regulation, the researchers artificially manipulated their activity using a chemogenetic approach. They found that activating the neurons led to a decrease in body temperature, while suppressing their activity led to an increase.

Overall, this study showed that EP3 neurons in the preoptic area play a key role in regulating body temperature by releasing GABA to send inhibitory signals to DMH neurons to control sympathetic responses. “It is likely that EP3 neurons in the preoptic area can precisely regulate signal strength to fine-tune body temperature,” said Prof. Nakamura, lead author of the study.

“For example, in a hot environment, signals are amplified to suppress sympathetic outputs, resulting in increased blood flow in the skin to facilitate the radiation of body heat to prevent heatstroke. 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. Furthermore, at the time of infection, PGE2 acts on EP3 neurons to suppress their activity, leading to the activation of sympathetic outputs to develop fever.”

The findings of this study could pave the way for the development of technology that artificially regulates body temperature, which could be used in a variety of medical fields. Interestingly, this technology may be useful in the treatment of obesity by keeping the body temperature slightly higher than normal to promote fat burning. “In addition, this technology could lead to new strategies for human survival in warmer global environments, which are becoming a serious global problem,” said Prof. Nakamura.

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