Researchers have discovered a new mechanism that regulates sleep in fruit flies that involves glial cells and their ability to manage a common ingredient in many energy drinks.

Sleep is an essential behavioral state in animals ranging from invertebrates to humans. It is critical for immune function, stable metabolism, brain repair, learning, and memory.

Over the course of a lifetime, more than 30 percent of people will experience a sleep disorder, which is associated with a number of diseases including Alzheimer’s, type 2 diabetes, and cardiovascular disease.

There is growing evidence that glial cells (or glia), long thought to simply “support” neurons in the brain, are actually quite important for diverse aspects of sleep regulation.

Sleep and wakefulness

For the study, researchers sought to identify new genes affecting sleep and wakefulness in Drosophila melanogaster (fruit flies), which share 75 percent of the genes that cause diseases in humans and display all of the behavioral and physiological characteristics of sleep.

They uncovered a gene that encodes the membrane transport protein known as excitatory amino acid transporter 2 or Eaat2.

Like humans, fruit flies are highly active during the day and sleep throughout the night. The authors found that fruit flies lacking the Eaat2 gene were excessively sleepy during the day.

When present, Eaat2 promoted wakefulness by limiting the length and intensity of sleep periods.

“Our research adds wakefulness to the growing list of fruit fly behaviors where glial cells play an important regulatory role, which includes circadian rhythms, movement, courtship, learning, and memory,” says Emilie Peco, a lead author of the study and a research associate in the lab of Don van Meyel, at the Research Institute of the McGill University Health Centre (RI-MUHC) and located at the Montreal General Hospital.

“Raising awareness about fundamental mechanisms of sleep is of general interest for society as millions of Canadians suffer from sleep disorders,” adds coauthor van Meyel, a professor of neurology at the McGill Centre for Research in Neuroscience and the BRaIN Program of the RI-MUHC.

“Daytime sleep in flies is more fragmented than nighttime sleep, but removal of Eaat2 caused their daytime sleep to mimic that which is typically observed only during the night,” says co-lead author Bethany A. Stahl, a postdoctoral fellow in the lab of coauthor Alex C. Keene, an associate professor of biological sciences in Florida Atlantic University’s Charles E. Schmidt College of Science and a member of the Jupiter Life Science Initiative.

Sleepy gene

“We think the identification of Eaat2 as a modulator of sleep will be important for researchers who study sleep regulation, sleep-dependent changes in metabolism, and perhaps physicians treating patients with sleep disorders. It suggests sleep researchers need to look beyond the role of neurons, to examine how glial cells control our sleep-wake regulation,” Keene says.

The researchers also discovered that Eaat2 promotes wakefulness by controlling the movement of taurine—an ingredient found in many energy drinks—into glial cells of the fly brain. Previous research showed Eaat2 transports taurine. To test if taurine might explain how Eaat2 affects sleep, Stahl fed it to some flies and found they slept more during the daytime than the control flies, but only if Eaat2 was present.

The study focused on fundamental mechanisms of sleep and glial cells in flies, but researchers expect their discovery will fuel research to determine if a mechanism involving the transport of taurine to and from glial cells might influence sleep in humans.

“It’s interesting to note that taurine is consistently elevated in blood and urine of sleep-deprived people, but it is unknown if taurine levels also change in the brain after sleep deprivation,” van Meyel says. “Even if you don’t indulge in energy drinks, there is a lot of taurine in the human brain, and what it does there is not understood all that well.”

The paper appears in Current Biology.

The National Institutes of Health, the Canadian Institutes of Health Research, the Natural Sciences and Engineering Research Council of Canada, and the Canada Foundation for Innovation funded the research.

Source: McGill University