January 20, 2009

Brain’s Support Cells Influence Sleep

Photo of a sleepy woman reaching for her alarm clock

Astrocytes, a type of support cell in the brain, may play an important role in influencing sleep, according to a study in mice. The results suggest a new approach for developing treatments for sleep disorders.

Why we sleep remains something of a mystery. Scientists know that too little sleep can affect the way we think, behave, form memories and perform at work and school. The brain keeps track of how much sleep we've gotten. When we haven't slept enough, we feel an increased need for sleep, which researchers call sleep pressure.

A chemical messenger called adenosine has long been known to help induce sleep. As adenosine builds up in the brain, we become sleepier. In fact, caffeine keeps us awake by blocking adenosine receptors in the brain. However, the source of adenosine and exactly how it functions to influence sleep and memory have been unclear.

Astrocytes are known to release a molecule called adenosine triphosphate (ATP) into the fluids surrounding brain cells, where it gets converted to adenosine. In a collaborative study, scientists at Tufts University School of Medicine and the University of Pennsylvania School of Medicine set out to investigate the role of astrocytes in regulating sleep. Their work was funded by NIH’s National Institute of Neurological Disorders and Stroke (NINDS), National Institute on Aging (NIA) and National Institute of Mental Health (NIMH).

The researchers explained in the January 29, 2009, issue of Neuron that they developed a method to temporarily block the release of ATP from astrocytes in the brains of mice, thus lowering levels of adenosine. The researchers then deprived the mice of sleep for short periods and evaluated them with behavioral tests and electrical recordings of brain activity.

The brain activity patterns in the mice with low brain adenosine showed reduced sleep pressure compared to control mice. After a period of sleep deprivation, these mice also needed less sleep time to recover than control mice did. The researchers next gave the mice a memory test that’s known to be sensitive to the effects of sleep pressure. Sleep deprivation impaired memory in the control animals, as expected, but memory in the mice with lower adenosine wasn’t affected by sleep deprivation.

This research is the first to show that the brain’s support cells can influence behavior. It “puts astrocytes at the heart of why we sleep,” says first author Dr. Michael Halassa of Tufts.

These mice might now prove useful for answering some long-standing questions about sleep, the researchers say.  For instance, since the mice are resistant to sleep deprivation, they could help researchers understand why some people need less sleep than others.

“Millions of Americans suffer from disorders that prevent a full night's sleep, and others—from pilots to combat soldiers—have jobs where sleepiness is a hazard. This research could lead to better drugs for inducing sleep when it is needed, and for staving off sleep when it is dangerous,” says Dr. Merrill Mitler, a program director with NINDS.

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