Scientists have discovered what amounts to a reset button for the internal body clock of mice. They say light triggers a process known as phosphorylation—when a phosphate combines with a key protein in the brain.
“This study is the first to reveal a mechanism that explains how light regulates protein synthesis in the brain, and how this affects the function of the circadian clock,” says Nahum Sonenberg, a professor in McGill University’s biochemistry department.
Jet lag, shift work, and exposure to light at night can affect the body clock and lead to sleep problems and other health issues.
To study the mechanism, researchers mutated the protein known as eIF4E in the brain of a lab mouse so that it could not be phosphorylated. Since all mammals have similar brain clocks, experiments with the mice give an idea of what would happen if the function of this protein were blocked in humans.
The mice were housed in cages equipped with running wheels. By recording and analyzing the animals’ running activity, the scientists were able to study the rhythms of the circadian clock in the mutant mice.
They found that the clock of mutant mice responded less efficiently than normal mice to the resetting effect of light. The mutants were unable to synchronize their body clocks to a series of challenging light/dark cycles—for example, 10.5 hours of light followed by 10.5 hours of dark, instead of the 12-hour cycles to which laboratory mice are usually exposed.
“While we can’t predict a timeline for these findings to be translated into clinical use, our study opens a new window to manipulate the functions of the circadian clock,” says Ruifeng Cao, a postdoctoral fellow in Sonenberg’s research group and lead author of the study published in Nature Neuroscience.
Shimon Amir, a professor in Concordia University’s psychology department and study coauthor, says the research could open a path to target the problem at its very source.
“Disruption of the circadian rhythm is sometimes unavoidable but it can lead to serious consequences. This research is really about the importance of the circadian rhythm to our general well-being. We’ve taken an important step towards being able to reset our internal clocks—and improve the health of thousands as a result.”
The Canadian Institutes of Health Research, the US National Institutes of Health, the Howard Hughes Medical Institute, the Fonds de recherche du Québec-Santé, and a Banting Postdoctoral Fellowship funded the study.
Source: McGill University