Sleep is a state of important behavior in animals ranging from invertebrates to humans. This is very important for immune function, stable metabolism, brain repair, learning and memory. During the lifetime, more than 30 percent of people will experience sleep disorders, which are associated with a number of diseases including Alzheimer's, type 2 diabetes, and cardiovascular disease.
There is increasing evidence that glia (or glia) cells, long thought to only "support" neurons in the brain, are actually quite important for various aspects of regulating sleep. Thanks to fruit flies (Drosophila melanogaster), a research team at Florida Atlantic University and McGill University in Quebec have discovered a new mechanism that regulates sleep that involves glia and their ability to manage common ingredients found in many energy drinks.
Fruit flies share 75 percent of the genes that cause disease in humans and display all behavioral characteristics and physiological sleep. For research published in the journal Biology at this timeThe researchers tried to identify new genes that affect sleep and wakefulness in fruit flies. With this approach, they found a gene that encodes a membrane transport protein known as excitation amino acid transporter 2 or Eaat2.
They found that Eaat2 promotes awareness in fruit flies by limiting the length and intensity of sleep periods. They also found that this was done by controlling the taurine movement – an ingredient found in many energy drinks – to glial cells from the fly's brain. In humans, taurine consistently increases in the blood and urine of people who are sleep deprived, but it is not known whether taurine levels also change in the brain after lack of sleep.
Like humans, fruit flies are very active during the day and sleep through the night. The authors found that Eaat2 disorders in fruit flies cause excessive daytime sleepiness.
"Sleep during the day is more fragmented than sleep at night, and disrupting Eaat2's function causes daytime sleep that mimics sleep usually observed only at night," said Bethany A. Stahl, Ph.D., lead author of the study and post-doctoral colleague at lab Alex C. Keene, Ph.D., a professor of biological sciences at FAU Charles E. Schmidt College of Science and member of the Jupiter Life Science Initiative (JSLI).
"About 70 million Americans suffer from sleep disorders, and we believe that raising awareness of the importance of understanding the basic mechanisms of sleep is an important problem globally," Keene said.
To determine the role of Eaat2 in metabolic regulation, researchers simultaneously measured sleep and CO? output of a single fly.
"We think the identification of Eaat2 as a sleep modulator will be important for researchers who study sleep regulation, sleep-dependent changes in metabolism, and maybe doctors treat patients with sleep disorders," Keene said. "This shows sleep researchers need to look beyond the role of neurons to examine how glial cells control our sleep-wake regulation."
The team found that Eaat2 works in specific glia cells from the fly's brain, not on neurons.
"Our research adds freshness to the growing list of fruit fly behaviors in which glial cells play an important role in regulation, which includes circadian rhythms, movement, courtship, learning and memory," said Emilie Peco, Ph.D., who co-led the study and was a colleague researcher in the lab Don van Meyel, Ph.D., a professor of neurology at McGill Center for Research in Neuroscience, and the BRaIN Program from the Research Institute of McGill University Health Center.
Eaat2 was previously shown to transport Taurine. So to test whether taurine might explain how Eaat2 affects sleep, Stahl feeds taurine in some flies and finds they sleep more during the day than flies control, but only if Eaat2 is present.
"Research led by Dr. Stahl and Dr. Peco focuses on the basic mechanisms of sleep and glial cells in flies, but we hope our findings will encourage research to determine whether a mechanism involving transport of taurine to and from glial cells can affect sleep in humans, "said van Meyel. "Even if you don't enjoy energy drinks, there is a lot of taurine in the human brain, and what it does there is not well understood."
Co-authors are Sejal Davla, Ph.D., McGill University; and Kazuma Murakami, Ph.D., and Nicholàs A. Caicedo Moreno, Ph.D., both at FAU. Collaboration between teams at FAU and McGill was developed organically from Keene's laboratory focus on sleep research and van Meyel's lab expertise in glial cells and membrane transport proteins.
This work is supported by the National Institutes of Health (NIH), the Canadian Institutes of Health Research (CIHR), Natural Sciences and the Canadian Technical Research Council, and the Canadian Foundation for Innovation.
JLSI aims to build educational skills and research in life sciences at FAU's John D. MacArthur Campus on Jupiter, and is a collaborative effort between Charles E. Schmidt College of Science and Harriet L. Wilkes Honors College.