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New study unlocks secret of internal body clock

Source:Ringier Medical Release Date:2015-04-30 438
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The mechanism in adjusting the circadian rhythm discovered by McGill and Concordia scientists could be of potential use in treating related disorders
NEW findings about the body clock’s molecular reset button could provide a potential treatment path for sleep disturbances and other abnormalities and conditions linked to jet lag, shift work, and exposure to light at night. 
 
The study conducted by an international team of scientists and published online April 27 in Nature Neuroscience reveals that the combination of a phosphate with a key protein in the brain resets the body’s internal clock. This process, which is known as phosphorylation, is triggered by light.
 
Researchers at McGill and Concordia universities in Montreal found out that in effect light stimulates the synthesis of specific proteins called Period proteins, which play a pivotal role in clock resetting and synchronizing the clock’s rhythm with daily environmental cycles. The findings reveal a potential target to treat a range of disorders, from sleep disturbances to other behavioral, cognitive, and metabolic abnormalities commonly associated with jet lag, shift work, and exposure to light at night, as well as with neuropsychiatric conditions such as depression and autism.
 
According to senior author Nahum Sonenberg, a professor in McGill’s Department of Biochemistry, “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.”
 
Ruifeng Cao, a postdoctoral fellow in Dr. Sonenberg’s research group and lead author of the study, said: “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.” 
 
Co-author Shimon Amir, professor in Concordia’s Department of Psychology, hoped 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,” Dr. Amir said.
 
To study the mechanism of the brain clock, the researchers mutated the protein known as eIF4E in the brain of a lab mouse so that it could not be phosphorylated. Because all mammals have similar brain clocks, the experiment with mice will shed light on probable outcomes if the function of this protein were blocked in humans.
 
In order to study the rhythms of the circadian clock in the mutant mice, the scientists recorded and analyzed the running activity of mice, which were housed in cages equipped with running wheels. The clock of mutant mice responded less efficiently than normal mice to the resetting effect of light, failing to synchronize their body clocks to a series of challenging light/dark cycles such as 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.
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