One of the biggest mysteries in sleep research has been how deep sleep, the most important for our body’s restorative needs, is regulated by the brain and how we can get more of it.
Also called “slow-wave sleep” or restorative sleep, this sleep cycle is imperative to restore our brain and body. But how this deep sleep is regulated in the brain has been of the most puzzling questions in sleep research. A new study led by Harvard Medical School researchers at VA Boston Healthcare System published in Nature Communications offers some critical clues into this longstanding secret and possibly some future relief for those who don’t get enough restorative rest.
“Our findings represent an important step forward in pinpointing the molecular basis of sleep regulation and point to an alternative pharmacologic strategy for promoting natural, restorative sleep,” Radhika Basheer, PhD, an associate professor of psychiatry at Harvard and researcher at Veterans Affairs Boston Healthcare System, told Sleepopolis.
Unlike the more active time of REM sleep which is crucial for cognitive growth, during deep sleep, your body slows down so functions like heartbeat, breathing, and eye movement slow and your body repairs and regrows tissue, builds bone and muscle, and strengthens the immune system.
Gene Editing and Deep Sleep
In this most recent study, scientists used CRISPR-Cas9 technology, the Harvard team focused on disrupting a gene in the thalamus of mice that is linked to a protein that binds to neurotransmitters that play a pivotal role in deep sleep. Existing drugs that promote sleep are tied to this protein. By disrupting this gene in the mice, scientists were able to boost the activity of delta waves and enhanced deep sleep in the animals.
The study identified an area in the brain that regulates delta waves (electrical signals transmitted across neurons) that arise during the deepest phases of relaxation. The signals are a hallmark of restorative sleep. And while many sleep medications help us to fall asleep, they don’t actually make sure we get enough of this deeper rest. Scientists hope with this study, new medications or therapies for deep sleep may be near.
The mice in the study had more delta activity throughout their non-REM sleep. In other words, the mice were getting more restorative sleep for their entire non-REM portion of the sleep cycle.
The advancement of gene editing with CRISPR enabled the team to target the molecule for the first time, Basheer added.
“We have identified a subunit of a receptor proteins…when disrupted, it can cause an increase in restorative sleep,” she noted. This is because the neurons are no longer inhibited, she added.
Now that they identified the molecule, they can target it pharmacologically, she said.
Current drugs such as Ambien decrease the activity of neurons, she said. Many people use melatonin, which is a hormone naturally produced in our bodies that works to assist our circadian rhythms and can help you get to sleep.
“None of them actually give you this restorative sleep. They aren’t capable of increasing delta waves,” Basheer said of the medications.
Moving Forward
Basheer said that the team plans to do more research on their discovery. The ultimate goal: To create sleep medications that can help people get deep sleep—not just help them fall asleep.
Researchers would need to replicate the findings in future animal models, Ritchie Brown, PhD, associate professor of psychiatry at Harvard and researcher at VA Boston, said in a statement. The findings could “set the stage” for a new class of sleep medicines, he added.
“This protein can be targeted by drugs,” Brown told Sleepopolis via email.
