Study identifies nerve cells important for maintaining normal body temperature in mammals

A research team at Nagoya University in Japan reported that a group of neurons, known as EP3 neurons, in the prefrontal area of ​​the brain play a key role in regulating body temperature in mammals. The discovery could pave the way for the development of a technology that artificially regulates body temperature to help treat heatstroke, hypothermia and even obesity. New research published in the journal scientific advance.

Body temperature in humans and many other mammals is regulated around 37°C (98.6°F), which optimizes all regulatory functions. When body temperature deviates significantly from the normal range, functions are impaired, which can lead to Sun stroke, hypothermia and, in the worst cases, death. However, these conditions can be treated if body temperature can be artificially adjusted to the normal range.

The brain’s temperature regulation center is located in the prefrontal area, the part of the hypothalamus that controls important body functions. For example, when the preoptic area receives signals from a mediator called prostaglandin E (PGE₂) is created in response to infection, this area commands an increase in body temperature to fight viruses, bacteria, and other disease-causing organisms.

However, it remains unclear exactly which neurons in the presynaptic region dictate the rise or fall of body temperature. To identify such neurons, Professor Kazuhiro Nakamura, Lecturer Yoshiko Nakamura and their colleagues at Nagoya University, in collaboration with Professor Hiroyuki Hioki at Juntendo University, conducted a historical study use mouse. They focused on EP3 neurons in the presynaptic region, which express PGE EP3 receptors₂and study the function of body temperature regulation.

Professor Nakamura and his colleagues first studied how the activity of EP3 neurons in the prefrontal region changes in response to changes in ambient temperature. The comfortable ambient temperature for mice is about 28°C. For two hours, the researchers exposed mice to cold (4°C), room (24°C) and hot (36°C) temperatures. The results showed that exposure to EP3 neurons was activated at 36°C, while exposure to 4°C and 24°C was not.

The team then observed the axons of EP3 neurons in the prefrontal region to determine where signals from EP3 neurons were transmitted. Observations show that nerve fibers distributed to different brain regions, especially the hypothalamus (DMH), which activates the sympathetic nervous system. Their analysis also showed that the substance that EP3 neurons use to signal to the DMH is Gamma-aminobutyric acid (GABA), a major inhibitor of neuronal excitability.

To further investigate the role of EP3 neurons in temperature regulation, the researchers artificially manipulated their activity using biochemistry. They found that activating the neurons resulted in a decrease in body temperature, while blocking their activity resulted in an increase in body temperature.

Taken together, this study suggests that EP3 neurons in the presynaptic region play a key role in regulating body temperature by releasing GABA to send inhibitory signals to neurons. the DMH to control sympathetic responses. “Perhaps, EP3 neurons in the presynaptic region can regulate precisely signal strength to regulate body temperature,” said Professor Nakamura, lead author of the study.

“For example, in a hot environment, signals are enhanced to block sympathetic outputs, leading to increased blood flow in the skin to facilitate the body’s heat radiation to prevent heat stroke. However, in cold environments, the signals are reduced to activate sympathetic output, which promotes heat production in brown adipose tissue and other organs to prevent hypothermia. Moreover, at the time of infection duplicate, PGE₂ acting on EP3 neurons to block their activity, leading to the activation of sympathetic outputs for fever.”

The findings of this study could pave the way for the development of technology to artificially regulate body temperature, which could be applied to many medical fields. Interestingly, this technology could be useful in the treatment of obesity, by keeping the body temperature slightly above normal to promote fat burning.

“Above all, this technology could lead to new strategies for humans to survive in a hotter global environment, which is becoming a serious problem worldwide,” said Professor Nakamura.

“Prostaglandin receptor expression EP3 .” neuron two-way control body temperature via tonic GABAergic signaling” published in scientific advance on December 23, 2022.