Humans and many other mammals maintain their body temperature at about 37°C (98.6°F), which is ideal for all regulatory processes. The functions are compromised when their body temperature noticeably deviates from the normal range, which could result in heat stroke, hypothermia, or, in the worst-case scenario, death. However, if body temperature can be artificially brought into the normal range, these problems might be addressed.
The preoptic area of the hypothalamus, which regulates the body’s essential processes, is where the brain’s temperature control center is located. For instance, the preoptic area sends a signal to the body to increase the temperature to combat viruses, germs, and other disease-causing organisms when it receives signals from the mediator prostaglandin E (PGE2), which is created in response to infections.
However, it is still unclear which neurons in the preoptic area release command to increase or decrease body temperature.
A research group at Nagoya University in Japan has identified critical neurons that maintain body temperature at 37°C in mammals. In their study, they reported that a group of neurons, called EP3 neurons, in the brain’s preoptic area play a key role in regulating mammalian body temperature.
In the study of rats, scientists mainly focused on EP3 neurons in the preoptic area, which express EP3 receptors of PGE2, and investigated the function for regulating body temperature.
Scientists first looked into how variations in environmental temperature affect the firing of EP3 neurons in the preoptic region. Rats like a temperature of about 28 °C for their habitat. The mice were subjected to cold (4°C), room (24°C), and hot (36°C) conditions for two hours. The findings demonstrated 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 region. The study found that nerve fibers are dispersed throughout the brain, especially in the dorsomedial hypothalamus (DMH), responsible for sympathetic nervous system activation. Gamma-aminobutyric acid (GABA), a potent inhibitor of neuronal excitation, is the molecule that EP3 neurons use for the signal transfer to DMH, according to their investigation.
Scientists experimentally altered EP3 neurons’ activity using a chemogenetic method better to understand these neurons’ function in temperature regulation. They discovered that raising body temperature resulted from suppressing the neurons’ activity while lowering it resulted from activating them.
Together, the results of this study demonstrated that EP3 neurons in the preoptic area are essential for controlling body temperature because they release GABA to communicate 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 the signal strength to fine-tune body temperature.”
“For example, in a hot environment, signals are augmented to suppress sympathetic outputs, resulting in increased blood flows in the skin to facilitate the radiation of the body’s heat 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. Furthermore, at the time of infection, PGE2 acts on EP3 neurons to suppress their activity, activating sympathetic outputs to develop a fever.”
The results of this study may lead to the creation of a technology that artificially modifies body temperature and has potential applications in numerous medical specialties. Interestingly, this technology may help treat obesity by maintaining a slightly elevated body temperature that encourages fat burning.
Prof. Nakamura said, “On top of that, this technology could lead to new strategies for the survival of people in hotter global environments, which are becoming a serious worldwide problem.”
- Yoshiko Nakamura, Takaki Yahiro et al. Prostaglandin EP3 receptor-expressing preoptic neurons bidirectionally control body temperature via tonic GABAergic signaling. Science Advances. DOI: 10.1126/sciadv.add5463