Canadian researchers are reporting the discovery of a "reset" switch for our body clocks that operates at the molecular level, a finding that could lead to treatments for conditions linked to disruptions of our circadian rhythm.
The discovery could yield a better understanding of a number of disorders linked to such disruptions, from sleep disturbances to behavioral or metabolic problems common with jet lag or shift work, they say.
Writing in the journal Nature Neuroscience, the scientists report their discovery that our body clocks get reset in a process known as phosphorylation, when a phosphate molecule combines with a particular brain protein - a process triggered by light.
That trigger results in the synthesis of key proteins known as Period proteins with a central role in synchronizing the body clock's rhythm to daily environmental cycles, the researchers explain.
"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 senior author Nahum Sonenberg, a biochemist at McGill University in Montreal.
Scientists at McGill and Concordia University, also in Montreal, mutated a protein in the brains of laboratory mice so that it was unable to be affected by phosphorylation. The process of phosphorylation, where a phosphate is added to a protein, turns many protein enzymes on and off, thereby altering their function and activity.
The researchers recorded the time the mice spent on running wheels in their cages as an indicator of the timing of their circadian clocks.
They found that the body clocks of the mutated mice were less efficient at resetting in response to artificial changes in their light/dark cycles, such as a change to 10.5 hours of light alternating with the same number of dark hours, as opposed to the 12-hour light-dark cycles laboratory mice normally live under.
While it may take a long time to translate such findings into possible clinical uses for treatment of circadian rhythm disorders in humans, the study suggests possible avenues for beneficial manipulation of the circadian clock, the researchers say.
In addition to jet lag and shift work or exposure to light at night, all of which can upset the circadian rhythm, there are indications our body clocks, when they go out of sync, can have an effect on neuropsychiatric conditions including depression and autism, the researchers point out.
"Disruption of the circadian rhythm is sometimes unavoidable but it can lead to serious consequences," says study co-author Shimon Amir of Concordia's Department of Psychology. "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."
