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Researchers believe they may have identified a new gene that has a direct impact on how much people sleep. The discovery came by studying a family who requires significantly less sleep than average (about 2 hours less).
"It's remarkable that we know so little about sleep, given that the average person spends a third of their lives doing it," said Louis Ptáček, a neurologist at the University of California, San Francisco (UCSF), and one of the paper's two senior authors. "This research is an exciting new frontier that allows us to dissect the complexity of circuits in the brain and the different types of neurons that contribute to sleep and wakefulness."
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Ptáček and UCSF geneticist Ying-Hui Fu, the paper's other senior author, are studying several families that require less sleep than average to function normally. Using genetic linkage studies and whole-exome sequencing, they discovered the gene ADRB1, which they believe is responsible for people requiring less sleep.
The researchers began their work by deciphering the role of the gene variant by studying its protein in the test tube. "We wanted to determine if these mutations caused any functional alterations compared with the wild type," Fu said.
"We found that this gene codes for ß1-adrenergic receptor, and that the mutant version of the protein is much less stable, altering the receptor's function. This suggested it was likely to have functional consequences in the brain."
The team of researchers then experimented with mice carrying a mutated version of the gene. The mice carrying the gene slept on average 55 minutes less than regular mice and the researchers further found that the gene was expressed at high levels in the dorsal pons.
This is an area of the brain stem involved in subconscious activities such as sleep. The researchers also found that normal ADRB1 neurons in this region were more active not only during wakefulness, but also during REM (rapid eye movement) sleep, but quiet during non-REM sleep.
"Another way we confirmed the role of the protein was using optogenetics," Fu explained. "When we used light to activate the ADRB1 neurons, the mice immediately woke up from sleep."
There are however limitations to using mice to study sleep. For instance, mice exhibit different sleep patterns than humans.
"But it's challenging to study sleep in humans, too, because sleep is a behavior as well as a function of biology," Fu added. "We drink coffee and stay up late and do other things that go against our natural biological tendencies."
Now, the researchers plan to study the ADRB1 protein in other parts of the brain and investigate other families for other genes that might play a role in sleep regulation. "Sleep is complicated," Ptáček noted.
"We don't think there's one gene or one region of the brain that's telling our bodies to sleep or wake. This is only one of many parts."
Fu said that the work could lead to the development of new types of drugs to control sleep regulation. "Sleep is one of the most important things we do," she said.
"Not getting enough sleep is linked to an increase in the incidence of many conditions, including cancer, autoimmune disorders, cardiovascular disease, and Alzheimer's."
The study is published in the journal Neuron.