WSU sleep researchers discover why some people may toss and turn more than others

A research team led by a Washington State University biochemist could help scientists shed light on why we need to sleep, and why some people have an easier time resting than others.

Jason Gerstner, a research assistant professor at WSU’s Elson S. Floyd College of Medicine, found that mutations in a “sleep gene” in the brain can cause humans, mice and fruit flies to have less restful sleep.

The results of the study were published in a peer-reviewed article in the journal Science Advances earlier this month.

It might sound odd, but scientists still aren’t sure why sleep is necessary. One theory is that sleep helps with memory formation and the brain’s growth and change: what scientists call neuroplasticity. Other theories maintain that sleep is restorative for the body and that it lowers metabolism, helping to conserve energy.

“We still don’t fully understand what biological function sleep is serving,” Gerstner said. “One of the ways we can get at answering that question is through examining neurobiological pathways.”

Much of Gerstner’s research has focused on a particular gene, FABP7, that’s been linked to sleep function. In previous research, Gerstner saw the gene’s expression cycles naturally during the day in mice, mirroring sleep-wake cycles.

For this study, Gerstner’s team looked at a sleep study of Japanese men, some of whom had a naturally occurring mutation in their FABP7 gene. Men with the mutation slept about as long as men without it, but their sleep was more fitful, with more bouts of time spent awake during the night.

Men with the mutation also reported more symptoms indicating clinical depression on an assessment, though neither group scored high enough to meet the criteria for depression. Gerstner said that suggests either the gene mutation itself or sleep disturbance might be linked to depression in some way.

There were no significant differences in health, age or sleepiness between the two groups of men.

The study showed similar restlessness in rats that had their FABP7 genes knocked out and in genetically engineered fruit flies with the same gene mutation. Because the mutation works the same way across species, it’s a promising finding for future research, and even for treatment of sleep disorders.

The FABP7 mutation causes the gene to create a different protein sequence. That affects which other proteins in the brain the sequences bind to, which in turn can influence a broad range of functions, like gene expression, inflammation and other brain functions.

The researchers also found the specific part of the brain, a star-shaped cell called an astrocyte, where FABP7 plays a role in sleep.

“Previously, those cells were thought to be support cells for neurons,” Gerstner said. Now, scientists are learning they’re important in their own right.

“This is some of the earliest evidence that astrocytes really play a role in sleep,” said Isaac Perron, a doctoral student in neurobiology at the University of Pennsylvania who worked with mice in the experiment.

Perron’s interest is in sleep and nutrition. Because the proteins coded by FABP7 bind with fatty acids like omega-3s, he thinks the gene might be a link in showing how the fatty acids we eat can influence brain functions, including sleep.

Jerry Yin, a professor of genetics at the University of Wisconsin-Madison, who worked on the fruit fly portion of the research, said finding a common pathway like FABP7 helps people looking at medications or gene therapies target their treatments.

Knowing FABP7 works in astrocytes helps researchers tailor their focus, since those cells are “where you’re likely to have an effect manipulating this gene,” Yin said.

Testing a therapy or medication is also easier because the FABP7 impact on sleep works in fruit flies and mice, both of which are commonly used in research.

“Since we’ve narrowed down particular protein expressed within astrocytes, it underscores the importance of these cells in regulating complex behavior across species,” Gerstner said.