AsianScientist (Nov. 11, 2016) – Researchers in Japan have identified two proteins that play key roles in regulating sleep in mice. Their work was published in Nature.
Mammalian sleep is made up of tightly controlled cycles of REM sleep and non-REM sleep. Recent research has identified neural networks in different parts of the brain that switch us between wakefulness, REM sleep and non-REM sleep; however, the molecular mechanism regulating these switches was unknown.
Using chemical mutagenesis to introduce random mutations into mice, researchers at the University of Tsukuba carried out a large-scale screening process that revealed roles for two proteins in regulating sleep need and maintaining periods of REM sleep. A mutant pedigree, named Sleepy, needed more sleep than others. This pedigree was shown to carry a mutation in the Sik3 gene, which encodes an enzyme expressed in neurons.
“We noticed that Sleepy mutants showed an exaggerated response to sleep deprivation,” said Dr. Hiromasa Funato, who was the first author of the study. “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.”
The researchers also identified a second sleep phenotype, called Dreamless, which exhibited a shortened and unstable REM sleep period. Dreamless mice carry a mutation in the Nalcn gene, which encodes an ion channel thought to control neuronal excitability. The Dreamless mutation causes increased ion conductance through the channel and increased activity of REM-terminating neurons, leading to increased REM sleep instability.
The article can be found at: Funato et al. (2016) Forward-Genetics Analysis of Sleep in Randomly Mutagenized Mice.
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Source: University of Tsukuba; Photo: Pixabay.
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