Many factors keep us from getting a good night’s sleep. Prime culprits include overnight flights across the ocean, graveyard shifts, and stress-induced insomnia. A new study from McGill and Concordia Universities gives hope, however, that these common sleep disturbances may one day be put to bed.
The Earth’s rotation is responsible for creating day and night, and the daily rhythms of all living beings. Mammals have a “circadian clock” in their brains that drive the daily rhythms in sleep and wakefulness, feeding and metabolism, and many other essential processes. Until now, however, the inner workings and molecular processes of this complex brain clock have eluded scientists.
The findings, published in Neuron, identify how a fundamental biological process called protein synthesis is controlled within the body’s circadian clock. The researchers hope their work will help shed light on future treatments for disorders triggered by circadian clock dysfunction, including jet lag, shift work disorders, and chronic conditions like depression and Parkinson’s disease.
“To understand and treat the causes and symptoms of circadian abnormalities, we have to take a closer look at the fundamental biological mechanisms that control our internal clocks,” says Dr. Shimon Amir, professor in Concordia University’s Department of Psychology.
Amir worked with Dr. Nahum Sonenberg, a James McGill professor in the Dept. of Biochemistry, Faculty of Medicine, at the Goodman Cancer Research Centre at McGill University, to study how protein synthesis is controlled in the brain clock. “We identified a repressor protein in the clock and found that by removing this protein, the brain clock function was surprisingly improved,” explains Dr. Sonenberg.
The circadian clocks of all mammals are similar, so the team was able to use mice to conduct their experiments. The mouse model used lacked this specific protein, known as 4E-BP1. The protein blocks the important function of protein synthesis. The mice that lacked this protein were able to overcome disruptions to their circadian clocks more quickly, the team found.
“In modern society, with the frequency of trans-time zone travel, we often deal with annoying jet lag problems, which usually require a couple of weeks of transition,” says Dr.Ruifeng Cao, a postdoctoral fellow who works with Drs. Sonenberg and Amir, “However, by inducing a state like jet lag in the mice lacking that protein, we found they were able to adapt to time zones changes in about half of the time required by regular mice.”
The research team also found, in mice lacking the protein 4E-BP1,there was a small increase in another small protein necessary for brain clock function, vasoactive intestinal peptide or VIP. This indicates to the researchers the functioning of the circadian clock could be improved by genetic manipulations, opening doors on new ways to treat circadian clock-related disorders.
“A stronger clock function may help improve many physiological processes, such as aging,” says Cao. “In addition, understanding the molecular mechanisms of biological clocks may contribute to the development of time-managing drugs,” Amir concurs, noting that “the more we know about these mechanisms, the better able we will be to solve problems associated with disruptions to our bodies’ internal clocks”.
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