UCLA scientists report the first evidence that a gene outside the brain controls the ability to rebound from sleep deprivation — a surprising discovery that could eventually lead to greatly improved treatments for insomnia and other sleep disorders that do not involve getting a drug into the brain.
The scientists report that increasing the level of Bmal1 — a critical master gene that regulates sleep patterns — in skeletal muscle makes mice resistant to sleep deprivation.
“When we first saw the importance of the muscle, we were surprised,” said senior author Ketema Paul, UCLA associate professor of integrative biology and physiology. “At first we didn’t believe it, so we repeated the experiment several times. We finally realized this is not a mistake; this is real.”
The research, published in the journal eLife, is the first evidence that a biological clock in the muscle can communicate with the brain, and is potentially good news for people who lose sleep because of factors including a crying newborn or a job that does not allow for normal sleep cycles, such as active military service.
Chronic sleep deprivation increases the risk for heart disease, stroke, diabetes, infectious diseases and other illnesses, said Paul, a neurobiologist and member of UCLA’s Brain Research Institute. Having a resistance to sleep loss may reduce the risk of getting these diseases, Paul said, and his team reports evidence that increased Bmal1 in the skeletal muscle may provide this resistance.
Turning Bmal1 off throughout the brain and body in mice, using a molecular genetic technique, impaired their ability to rebound from sleep deprivation, the researchers report. Restoring the gene in the skeletal muscle enabled the mice to rebound from the sleep deficit, while restoring the gene in the brain, surprisingly, did not. Increasing the level of this gene in skeletal muscle also made mice less sleepy after longer periods of sleep deprivation. The researchers increased the level by genetically inserting extra copies of the gene into the genome of the mice.
“We show that not only is Bmal1 responsible for the ability to recover from sleep loss, but also that Bmal1 expression in the skeletal muscle is responsible for that process,” Paul said. “When we increased Bmal1 in the skeletal muscle, the mice were able to tolerate more sleep loss. That suggests the skeletal muscle is directly communicating with the…