Neurons responsible for maintaining body temperature identified : Study

TOKYO: Scientists have identified neurons responsible for regulating the body temperature of mammals, paving the way for technological development which can artificially adjust it to help treat heat stroke, hypothermia, and even obesity, according to a new study.

A research group at Nagoya University, Japan, has reported that a group of neurons, called EP3 neurons, in the preoptic area of the brain play a key role in regulating body temperature in mammals. The preoptic area is a 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) that is produced in response to infections, the preoptic area releases a command to raise body temperature to fight against viruses, bacteria, and other disease-causing organisms.

The findings are published in the journal Science Advances.

Body temperature in humans and many other mammals is regulated at around 37 degrees Celsius, or 98.6 degrees Fahrenheit, which optimizes all regulatory functions. When their body temperature noticeably deviates from the normal range, the functions are impaired, which could lead to heat stroke, hypothermia, and, in the worst case, death. However, these conditions might be treated if body temperature can be artificially adjusted to the normal range.

It was unclear exactly which neurons in the preoptic area release commands to increase or decrease body temperature.

To identify these neurons, Professor Kazuhiro Nakamura and his team conducted a study using rats. They focused on EP3 neurons in the preoptic area, which express EP3 receptors of PGE2, and investigated the function for regulating body temperature, the study said.

Professor Nakamura and his colleagues first investigated how the activity of EP3 neurons in the preoptic area varies in response to changes in ambient temperature, the study said.

A comfortable environmental temperature for rats is around 28 degrees Celsius. For two hours, the researchers exposed the rats to cold (4 degrees Celsius), room (24 degrees Celsius) and hot (36 degrees Celsius) temperatures.

Results showed that exposure to 36 degrees Celsius activated EP3 neurons, while exposure to 4 and 24 degrees Celsius did not.

The group then observed nerve fibers of EP3 neurons in the preoptic area to identify where the signals from EP3 neurons are transmitted. The observation revealed that nerve fibers are distributed to various brain regions, particularly to the dorsomedial hypothalamus (DMH), which activates the sympathetic nervous system.

The sympathetic nervous system is constantly active at a basic level to maintain homeostasis, which is the condition of optimal functioning for the organism and includes many variables, such as body temperature and fluid balance.

The team's analysis also showed that the substance that EP3 neurons use for the signal transmission to DMH is gamma-aminobutyric acid (GABA), a major inhibitor of neuronal excitation, the study said.

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

Taken together, 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.

''Probably, EP3 neurons in the preoptic area can precisely regulate the signal strength to fine-tune body temperature,'' said Nakamura, the lead author of the study.

''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, resulting in activation of sympathetic outputs to develop fever,'' said Nakamura.

Technological development capable of artificially adjusting body temperature can be applied to a wide range of medical fields such as in the treatment of obesity, by keeping body temperature slightly higher than normal to promote fat burning, the study said.

''On top of that, this technology could lead to new strategies for survival of people in hotter global environments, which is becoming a serious worldwide problem,'' said Nakamura.