Circadian clocks, which regulate the metabolic activities of all living creatures over a period of about 24 hours, are one of the most basic biological mechanisms. In humans, their disorder is the cause of many metabolic diseases such as diabetes or severe liver diseases.
Although scientists have been studying this device for several years, little is known about how it works. Thanks to a bioluminescence-based observation device, a research team from the University of Geneva (UNIGE) was able to show that cells that make up a particular organ can be at a level, even without a central brain clock or any other clocks in the body. .
In fact, the scientists have been able to restore circadian activity in the liver in completely arrhythmic mice, indicating that specific neurons do not have the ability to coordinate. Results are available in the journal Gene and Development.
For a long time, the scientific community believed that circadian rhythms were completely controlled by a central clock located in the brain, before they discovered, a few years ago, that every cell had a small molecular clock.
Nonetheless, the brain clock was considered essential for the synchronization of all peripheral clocks, ”said Ueli Schibler, an honorary professor at the UNIGE Faculty of Science, who began the work.
However, conventional search engines did not allow us to examine the effectiveness of this idea. In fact, to do that, we need to be able to continue in real time, over a relatively long period of time, the expression of an animal ‘s circadian genes with or without active brain clock. “
Flore Sinturel, Frst Study Author and R.esearcher, Department of Medicine, UNIGE Faculty of Science
Bioluminescence to study circadian rhythms
As early as 2013, Professor Schibler’s team developed a completely new technology, now commercially available, that makes it possible to monitor the activity of a particular organ and the circadian rhythms that control it.
“We were inspired by the principle of bioluminescence seen in fireflies, for example,” he explains. “Our mice carry a circadian express gene that produces an enzyme, luciferase. We then add luciferin to their drinking water, a substance which, when oxidized by the luciferase, causes photon emission. “Light is then captured by a photomultiplier which records the number of photons that are emitted per minute and thus detect the expression of the circadian narrator gene over time.
Liver clock cells are connected to each other without receiving time cushions
After removing the central clock, scientists saw that all the clocks in the body are at different levels. However, at the level of one organ – the liver in this case – the mice maintain a strong and coordinated circadian rhythm.
Thus, while the clock in the middle can synchronize all the organs at the same rate, the cells communicate enough to maintain a coordinated rhythm within a single organ. “While neurons were thought to have only strong enough connections to ensure this circadian coordination, we are now showing that this is not true,” says Flore Sinturel. “This puts the singularity of the clock in the middle in view.”
The scientists then confirmed their discovery: in arrhythmic mice, ie mice with no circadian clocks at all, the researchers succeeded in restoring rhythm in the liver alone, without touching the other organs.
“This allows us to show that a clock restored in one organ works and that there are rhythms, even without the other clocks in the body,” she explains. They now want to understand how these cells stay at the same level when they receive no information, either from the brain or from other external signals.They have the idea that it is a form of pairs, in the form of exchange of molecules between these different cells.