Overworked Brains Release Adenosine To Slow Cells, Trigger Sleep, UT Southwestern Researchers Find

When cells in a certain part of the brain become overworked, a compound in the brain kicks in, telling them to shut down. This causes people to become drowsy and fall asleep. Alter that natural process by adding coffee or tea, and the brain compound - called adenosine - is blocked, and people stay awake.

These findings, available online and in the April 21 issue of the journal Neuron, offer new clues regarding the function of the brain in the body's natural sleep process, as well as potential targets for future treatments for insomnia and other sleep problems.

Prolonged increased neural activity in the brain's arousal centers triggers the release of adenosine, which in turn slows down neural activity in the arousal center areas. Because the arousal centers control activity throughout the entire brain, the process expands outward and causes neural activity to slow down everywhere in the brain.

"Insomnia and chronic sleep loss are very common problems," said Dr. Robert W. Greene, professor of psychiatry and senior author of the study. "In addition, all the major psychiatric disorders, including depression, schizophrenia and post-traumatic stress disorder have sleep disruption as a prominent symptom.

"If we can understand better some of the factors involved in what makes us normally fall asleep, we can start to understand what might be going wrong when we don't."

Showing that increased brain cell activity triggers drowsiness also explains how caffeine works in helping people fight sleep.

"We knew that coffee kept us awake," Dr. Greene said. "Now we know why: Coffee and tea are blocking the link between the prolonged neural activity of waking and increased levels of adenosine in cells, which is why they prevent us from getting drowsy."

Past studies by Dr. Greene and his colleagues have shown that adenosine may act as a "fatigue factor." When adenosine levels increase in the arousal centers -- as happens with prolonged waking --  mammals tend to fall asleep. But what hasn't been known before is what triggers the release of adenosine to induce sleep.

"Neurons in the brain do things -- such as talk to each other, process information and coordinate body activities - which are called neural activity," said Dr. Greene.  "When they do this over a long period of time, more and more adenosine is released and feeds back onto the cells to quiet them down. It's like telling them: 'You guys have worked too hard; take it easy, and refresh yourselves.' "

"What we have shown in our study is that it's this prolonged neural activity of being awake that causes adenosine levels to go up, which in turn makes a person feel drowsy. It's the brain's way of achieving a proper balance between the neural activity of waking and the need for sleep. If something goes wrong with this adenosine system, you may end up with insomnia."

Other UT Southwestern researchers on the study were Dr. David Chapman, a postdoctoral researcher in psychiatry, and Dr. Dario Brambilla, a former postdoctoral researcher in psychiatry, now at the University of Milan Medical School in Italy.

The study was supported by the National Institute of Mental Health and the Department of Veterans Affairs.