By analyzing the genes and brain activity of more than 8,000 mice, researchers have identified two genes that control deep sleep and dreaming, opening the door to new treatments for sleep disorders.
In a study published in the journal Nature, investigators describe the discovery of a gene that regulates the amount of rapid eye movement (REM) sleep in mammals, as well as a gene that controls the amount of non-rapid eye movement (NREM) sleep.
According to the National Sleep Foundation, REM is a recurring sleep stage that makes up around 25 percent of a typical night’s sleep.
REM is described as a period of sleep involving intense brain activity that is comparable to waking-state brain activity. Vivid dreaming is most likely to occur during REM sleep.
NREM accounts for the remaining 75 percent of sleep, and it is characterized by a reduction in brain activity. NREM sleep consists of three stages: drowsiness, light sleep, and slow wave sleep – the deepest sleep stage, where no eye movement or muscle activity occurs.
Both REM and NREM are considered important for health and well-being, aiding tissue growth and repair and ensuring the brain and body are able to function effectively during the day.
However, the underlying mechanisms that regulate both of these sleep stages have been unclear. Now, for the first time, researchers have pinpointed two genes that they believe control REM and NREM sleep.
For their study, co-author Joseph S. Takahashi, of the O’Donnell Brain Institute at the University of Texas (UT) Southwestern Medical Center in Dallas, and colleagues introduced random mutations to the genes of more than 8,000 mice.
The team them used electroencephalogy (EEG) to monitor the brain waves of the rodents, with the aim of seeing whether any of the genetic mutations they introduced affected their sleep.
The researchers identified two genes – Salt-Inducible Kinase 3 Sik3 (Sik3) and Sodium Leak Channel Non-selective (Nalcn) – that appear to play a role in REM and NREM sleep.
Mice that had a mutation in the Sik3 gene – referred to as “Sleepy” mice – were found to have 50 percent more NREM sleep than mice without this mutation, the team reports.
“We noticed that Sleepy mutants showed an exaggerated response to sleep deprivation,” notes first author Hiromasa Funato, of the University of Tsukuba in Japan. “Examining the brains of sleep-deprived mice revealed changes in the phosphorylation of amino acids within the SIK3 protein. These changes were disturbed by the Sik3 mutation in Sleepy mice, which is why they have an increased sleep need.”
Additionally, they found that mice with a mutation in the Nalcn gene – named “Dreamless” mice – were found to have much less REM sleep than mice without a Nalcn gene mutation.
“The Dreamless mutation causes increased ion conductance through the channel and increased activity of REM-terminating neurons, which is compatible with REM sleep instability,” explains co-author Chika Miyoshi, also of the University of Tsukuba.
All in all, the researchers believe their findings suggest Sik3 and Nalcn play significant roles in mammalian sleep, and the discovery of these genes may pave the way for new treatments for sleep disorders.
The National Sleep Foundation recommend that adults aged 18-64 get around 7-9 hours of sleep daily, while adults aged 65 and older should aim to get around 7-8 hours of sleep.
However, according to the Centers for Disease Control and Prevention (CDC), more than 25 percent of people in the United States often fail meet the sleep recommendations, and around 50-70 million American adults have some form of sleep disorder.
According to the researchers, it is possible that proteins produced by the Sik3 and Nalcn genes could be drug targets for sleep disorders.
“At least in theory, this study opens up future possibilities to create new sleep-regulating drugs, but doing so will occur in the distant future,” notes senior author Dr. Masashi Yanagisawa, professor of molecular genetics at UT Southwestern.
What is more, the researchers believe their study may fuel the discovery of other genes that play important roles in mammalian sleep.
“We hope that the discovery of these key genes is just the beginning of our long journey into the blackbox of sleep regulation. It is amazing that we know almost nothing about the simple question of what is ‘sleepiness’ physically in our brain. We will start from these genes and try to solve the great mystery.”
Dr. Masashi Yanagisawa