The Brain

Muscle Protein, Not Just Brain, Involved In Sleep Regulation

Investigations into the secrets of sleep often start and stop with the brain – somewhere buried inside the wrinkles and folds of our three-pound organ is the answer to our dysfunctional sleep. Yet this fixed focus may be missing a vital piece of the puzzle. New research suggests that a key component of sleep may lie in our muscles instead. 

Scientists at UCLA found that a skeletal muscle protein lessens sleep deprivation in mice. The finding could lead to treatments for insomnia and sleep disorders that don’t involve breaking through the blood-brain barrier, the brain’s high-end security system that often vexes scientists with its ability to thwart drug treatments from accessing the brain. 

“This finding is completely unexpected and changes the ways we think sleep is controlled,” added co-author Joseph Takahashi, chairman of neuroscience at UT Southwestern Medical Center, in a statement.

For the study, published in eLife, the team manipulated levels of the protein Bmal1. Mice with higher levels of the protein in their skeletal muscles recovered more swiftly from sleep deprivation than those with less. According to the team, this is novel evidence that a biological clock protein in muscle can communicate with the brain and influence sleep patterns.

What’s more, high levels of Bmal1 in the brain had no effect on the mice. “I think one of the reasons we’ve missed this is because we spent so much time looking in the brain,” said senior author Ketema Paul of UCLA.

To explore this link, the mice were kept awake for 24 hours, with their brain activity measured with an electroencephalogram. Those with almost six times as much Bmal1 in their muscle were significantly less sleepy than those with less of the protein.

The team then removed Bmal1 from the mouse genome and found that this did indeed influence the mice’s sleep behavior. Those without this integral component no longer rebounded quickly from sleep deprivation. Upon reintroduction, however, recovery rate was restored.

The next logical question is how safe is it to increase Bmal1 levels? If upping the protein reduces the effects of sleep deprivation, are there unforeseen consequences elsewhere? Over the course of three years, the team tested for this but have yet to find any negative consequences.

Sleep is a clearly crucial player in our overall health, with more than a third of Americans not getting enough sleep, according to the Centers for Disease Control and Prevention. This puts people at an increased risk of obesity, stroke, high blood pressure, heart disease, and mental decline. 

The study suggests there could be new, yet undiscovered therapeutic pathways for treatments into insomnia and sleep disorders that don’t require breaking through the blood-brain barrier. For now, though, further research is needed to fully understand the link and whether the same influence is found in humans. 

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