HONG WANG AND J. SIEMENS
Certain nerve cells in a mouse’s brain may act like mini-fridges. And that’s a good thing.
These newfound “refrigerator” cells hum along in the brains, a new study in mice finds. When they turn on, they can bring the body’s temperature down dramatically — and perhaps even prevent high fevers.
The results “are totally new and very important,” says Andrej Romanovsky. He works at the Barrow Neurological Institute in Phoenix, Ariz. As a physiologist (Fis-ee-OL-oh-gizt), he studies how the body functions. Of the new findings, he says, “The implications are far-reaching.” This research reveals which cells act as a thermostat for the body.
The findings also may offer scientists new ways to explore how body temperature and metabolism are connected. Metabolism is a term scientists use to describe the chemical reactions living cells perform to keep their host alive. These reactions affect how the body uses food as fuel, and how much weight an organism carries. So the new work might reveal something about obesity — and ultimately about lifespan.
To start the study, scientists had to figure out where to scout for those so-called fridge cells. They had good reason to think they sat in a small patch of nerves in the middle of the brain. This patch of brain real estate is called the hypothalamus (Hy-poh-THAAL-uh-mus). Temperature fluctuations in a part of this tissue — the preoptic area — were known to prompt the body to return to its baseline temperature. They tell the body when to conserve heat and when to shed it. But the actual cells that served as the thermostat remained unknown. The new study uncovers their identity. They’re cells known by a protein, TRPM2, that they wear on their outer surface
Shaun Morrison is a physiologist at Oregon Health & Science University in Portland. “Overall,” he says, “this is a major discovery in the field of thermoregulation.” As the word implies, this field involves the regulation of a body’s temperature — especially the temperature at its core.
Jan Siemens, who led the new study, works at the University of Heidelberg in Germany. As a neurobiologist, he investigates the actions of nerve cells. In the new experiments, he and his colleagues looked at certain molecules. Called TRP channels, these molecules are proteins that sit on the outer layer of a cell. They help sense a variety of stimuli. What they sense can include anything from a source of pain (such as tear gas) to something cool (like menthol). The researchers ran tests on different types of these nerve cells in lab dishes. One protein seemed to respond to heat. The scientists refer to this protein as TRPM2.
Next, the researchers wanted to see what the protein did in animals. So, they gave mice fevers by injecting “heat up” molecules into their brains' hypothalamus. Mice lacking TRPM2 became about 1 degree Celsius (1.8 degrees Fahrenheit) warmer than mice with the protein. That suggested that TRPM2 might help counter overheating.
“We like to think of it as an emergency brake,” Siemens says. It prevents a fever from getting too hot. He and his team published their findings online August 25 in Science.
Romanovsky cautions that it’s not easy to understand what to make of the fever results. Indeed, in some tests, mice without TRPM2 didn’t run hotter fevers than other mice. More experiments are needed to clarify how these nerve cells affect the risk of fever, he says.
From hot to cold
Siemens and his colleagues didn’t study only how nerve cells affect fever. They also looked at how the cells affect body cooling. To do this, the team used a genetic trick to take more direct control of cells with TRPM2 in the thermostat zone of the brain.
When these cells were prevented from firing off signals, the mice heated up slightly. And when the cells were prompted to fire off lots of signals, the mice grew downright cold. How cold? A mouse’s normal body temperature hovers around 37° C (98.6 °F). After a burst of activity from TRPM2 nerve cells, body temperatures in a mouse dropped by about 10 degrees Celsius (18 degrees Fahrenheit. And they stayed this cool for about half a day.
Recalls Siemens, seeing that “was really a ‘wow’ experience.”
The team also watched how the mice shed their body heat. For this, the researchers used an infrared — or heat — camera. When nerve cells sent out their signals to chill, the mice started dumping body heat.
The first change: Their bodies shunted warm blood to the surface of their skin. This warmed their paws and tails — body parts from which heat easily escapes. Those cameras revealed hot tails soon after the nerve cells turned on. They also revealed that the animals’ sleeping areas warmed as the mice transferred heat from their bodies to their beds. The cooling animals “were actually warming up their surroundings,” Siemens reports.
More work is needed to say whether similar cells help cool people.
For now, scientists don’t have good drugs that affect TPRM2. One day, however, these data point toward ways to induce drastic temperature drops from inside the body. Why? Doctors sometimes use ice packs and cooling blankets to chill people after they have experienced cardiac arrest (a sudden, unexpected loss of heart function, breathing and consciousness). In these cases, an internal cooldown might be more effective.
And the new research may help pave the way to do that.
(for more about Power Words, click here)
cardiac arrhythmia An irregular heartbeat. There are several types of arrhythmias; the heart can beat too fast, too slow or in a pattern that’s not normal. Some arrhythmias are mild and have little if any effect; others can be life-threatening.
cell The smallest structural and functional unit of an organism. Typically too small to see with the naked eye, it consists of watery fluid surrounded by a membrane or wall. Animals are made of anywhere from thousands to trillions of cells, depending on their size. Some organisms, such as yeasts, molds, bacteria and some algae, are composed of only one cell.
chemical A substance formed from two or more atoms that unite (become bonded together) in a fixed proportion and structure. For example, water is a chemical made of two hydrogen atoms bonded to one oxygen atom. Its chemical symbol is H2O. Chemical can also be an adjective that describes properties of materials that are the result of various reactions between different compounds.
chemical reaction A process that involves the rearrangement of the molecules or structure of a substance, as opposed to a change in physical form (as from a solid to a gas).
colleague Someone who works with another; a co-worker or team member.
conserve To protect, as from loss or degradation.
control A part of an experiment where there is no change from normal conditions. The control is essential to scientific experiments. It shows that any new effect is likely due only to the part of the test that a researcher has altered. For example, if scientists were testing different types of fertilizer in a garden, they would want one section of it to remain unfertilized, as the control. Its area would show how plants in this garden grow under normal conditions. And that give scientists something against which they can compare their experimental data.
core In geology, Earth’s innermost layer. Or, a long, tube-like sample drilled down into ice, soil or rock. Cores allow scientists to examine layers of sediment, dissolved chemicals, rock and fossils to see how the environment at one location changed through hundreds to thousands of years or more.
fuel Any material that will release energy during a controlled chemical or nuclear reaction. Fossil fuels (coal, natural gas and petroleum) are a common type that liberate their energy through chemical reactions that take place when heated (usually to the point of burning). But food is also a fuel.
genetic Having to do with chromosomes, DNA and the genes contained within DNA. The field of science dealing with these biological instructions is known as genetics . People who work in this field are geneticists .
host (in biology and medicine) The organism in which another lives. Humans may be a temporary host for food-poisoning germs or other infective agents.
hypothalamus A region of the brain that controls bodily functions by releasing hormones. The hypothalamus is involved in regulating appetite through release of appetite-suppressing hormones.
induce To produce or cause something to happen. In physics, electromagnetic induction is the production of electricity with varying magnetic fields.
metabolism The set of life-sustaining chemical reactions that take place inside cells and bigger structures, such as organs. These reactions enable organisms to grow, reproduce, move and otherwise respond to their environments.
molecule An electrically neutral group of atoms that represents the smallest possible amount of a chemical compound. Molecules can be made of single types of atoms or of different types. For example, the oxygen in the air is made of two oxygen atoms (O2 ), but water is made of two hydrogen atoms and one oxygen atom (H2O).
nerve A long, delicate fiber that communicates signals across the body of an animal. An animal’s backbone contains many nerves, some of which control the movement of its legs or fins, and some of which convey sensations such as hot, cold, pain.
neurobiologist Scientist who studies cells and functions of the brain and other parts of the nervous system.
obesity Extreme overweight. Obesity is associated with a wide range of health problems, including type 2 diabetes and high blood pressure.
organism Any living thing, from elephants and plants to bacteria and other types of single-celled life.
physiologist Scientists who study the branch of biology that deals with the bodies of healthy organisms function under normal circumstances.
proteins Compounds made from one or more long chains of amino acids. Proteins are an essential part of all living organisms. They form the basis of living cells, muscle and tissues; they also do the work inside of cells. The hemoglobin in blood and the antibodies that attempt to fight infections are among the better-known, stand-alone proteins. Medicines frequently work by latching onto proteins.
risk The chance or mathematical likelihood that some bad thing might happen. For instance, exposure to radiation poses a risk of cancer. Or the hazard — or peril — itself. Among cancer risks that the people faced were radiation and drinking water tainted with arsenic.
thermostat A temperature sensor that allows a system to know when a change — either heating or cooling — is called for.
tissue Any of the distinct types of material, comprised of cells, which make up animals, plants or fungi. Cells within a tissue work as a unit to perform a particular function in living organisms. Different organs of the human body, for instance, often are made from many different types of tissues. And brain tissue will be very different from bone or heart tissue.