Scientists discover reset ''button'' for body clock

Toronto, April 28

Scientists have found a molecular reset button for our internal body clock, a discovery that may allow for new treatments of sleep disorders and cognitive and metabolic abnormalities, commonly associated with jet lag and shift work.

According to the study led by researchers at McGill and Concordia universities in Montreal, the body's clock is reset when a phosphate combines with a key protein in the brain.

This process, known as phosphorylation, is triggered by light.

In effect, light stimulates the synthesis of specific proteins called Period proteins that play a pivotal role in clock resetting, thereby synchronising the clock's rhythm with daily environmental cycles.

“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,” said senior author Nahum Sonenberg, a professor in McGill's Department of Biochemistry.

In order to study the brain clock's mechanism, the 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 analysing the animals' running activity, the scientists were able to study the rhythms of the circadian clock in the mutant mice.

The clock of mutant mice responded less efficiently than normal mice to the resetting effect of light.

The mutants were unable to synchronise 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," said Ruifeng Cao, a postdoctoral fellow in Sonenberg's research group and lead author of the study.

The study is published in the journal Nature Neuroscience. PTI