A body temperature of around 37 degrees Celsius is vital for most mammals. But how is this delicate balance regulated – for example, when we are in very cold or very warm environments? A research team is now investigating this in rats. Accordingly, the so-called EP3 neurons in the preoptical area of the brain play a key role. They ensure the appropriate body reactions to heat and cold and are also involved in the development of fever.
Most mammals have a body temperature of around 37 degrees Celsius. If the body temperature deviates from the normal range by a few degrees, many vital functions are impaired. Both hypothermia and heat stroke can have serious consequences, including death. In order to avoid such states, our body has a sophisticated temperature control system. When it is hot, the blood flow to the skin increases in order to dissipate heat in this way, and our body cools down additionally with the help of sweating. When it's cold, on the other hand, the superficial blood vessels constrict and the burning of fat for heat production is boosted. These reactions are controlled by the so-called pre-optic area of the brain, part of the hypothalamus. How exactly the regulation works, however, was previously unclear.
Rats in heat and cold
A team led by Yoshiko Nakamura from Nagoya University in Japan has now identified the neurons responsible for regulating body temperature and uncovered the principles on which they work. To do this, they exposed rats to different ambient temperatures. For two hours at a time, they placed the animals in a cage that was cooled to four degrees Celsius or heated to 36 degrees Celsius or in which the room temperature was 24 degrees Celsius, which was comfortable for rats.
The researchers observed the activity of the neurons in the preoptic area of the rats' brain. They focused on the so-called EP3 neurons. Previous studies had already suggested that these could be involved in thermoregulation. Among other things, they react to the messenger substance prostaglandin E2 in infections and cause fever in this case. However, there has not yet been any evidence that they are also involved in the regulation of normal body temperature, or any insight into how they work.
control through inhibition
The current study now shows that the EP3 neurons do indeed play a crucial role in maintaining body temperature. "If the rats were exposed to heat, this significantly increased the activity of the EP3 neurons," report Nakamura and her colleagues. At room temperature and cold, however, this was not the case. Further investigations revealed that the EP3 neurons send signals via the messenger substance gamma-aminobutyric acid (GABA) to other nerve cells, including those areas of the hypothalamus that activate the sympathetic nervous system.
GABA is one of the most important inhibitors for neuronal excitation. So when the EP3 neurons are activated and release GABA, this inhibits the sympathetic nervous system. While the sympathetic nervous system, among other things, causes the superficial blood vessels to contract, the inhibition causes these blood vessels to expand and more heat to be released. In this way, our body reduces the risk of heat stroke.
Thermoregulation artificially manipulated
The researchers also found that the EP3 neurons show some basal activity at room temperature, thereby slightly and persistently inhibiting the sympathetic system. "It's likely that the EP3 neurons in the preoptic region can finely regulate signal strength to fine-tune body temperature," says Nakamura. In a cold environment, the signal strength decreases, allowing the sympathetic nervous system to become more active. "This promotes heat production in brown adipose tissue and other organs to prevent hypothermia," explains Nakamura. The activity of the EP3 neurons is also throttled with the help of prostaglandin E2 during an infection, so that the sympathetic system can increase the body temperature.
The researchers substantiated their results by artificially altering the activity of the EP3 neurons. And indeed: Artificial activation of this group of nerve cells also set mechanisms in motion that lower body temperature, while inhibition of the EP3 neurons led to an increase in body temperature. From the researchers' point of view, the findings could help to develop technologies with which the control of body temperature can be manipulated. Theoretically, it would be conceivable to set the body temperature a little higher than normal in order to promote fat burning. "In addition, this technology could lead to new strategies for human survival in hotter global environments, which are becoming a serious problem worldwide," said Nakamura.
Source: Yoshiko Nakamura (Nagoya University, Japan) et al., Science Advances, doi: 10.1126/sciadv.add5463