Sleepy Heads: Low fuel may drive brain’s need to sleep

Why animals must sleep is a mystery to scientists. But a new study suggests that a vital function of sleep is to refuel the brain.

Canadian scientists report that energy stores in the brains of rats decline when the animals are forced to stay awake and the stock rebuilds while the animals sleep. The findings support a hypothesis that dwindling energy stores in the waking brain induce sleep (SN: 5/24/97, p. 316:

Most past attempts to test the hypothesis failed because there was no good way to measure brain-energy stores, says Jonathan D. Geiger of the University of Manitoba in Winnipeg, a coauthor of the report. Glycogen, the complex carbohydrate that provides short-term energy storage for brain and muscle, rapidly deteriorates in tissue taken from an animal. So, scientists can’t measure glycogen concentrations accurately. Geiger and his colleagues dodged this problem by applying powerful microwaves to rat brains, killing the animals and instantly inactivating the enzymes that break down glycogen after death. The scientists then removed the rats’ brains and measured glycogen concentrations.

The scientists tested some rats at their usual bedtime and kept others awake for 6, 12, or 24 hours by gently playing with them. The scientists then microwaved and removed each animal’s brain and measured brain glycogen. They found that glycogen concentrations were 38 percent lower in the rats that were sleep-deprived for 12 or 24 hours compared with the other two groups.

When other rats deprived of sleep for 12 or 24 hours were permitted to sleep without restriction, their brain glycogen rebounded to above-normal concentrations.

The brain may be bracing itself for future bouts of sleep deprivation, the authors speculate in the July 1 Journal of Neuroscience. Skeletal muscles similarly overload glycogen when they’re recovering from strenuous exercise, Geiger notes.

The scientists treated sections of frozen brain tissue from the rats with a chemical that stains areas of high glycogen concentration. They found that glycogen was distributed unevenly in the brains of rats both with and without sleep deprivation. During sleeplessness, brain areas varied in their decreases in glycogen.

“This work opens a whole new area of sleep research, as well as research in understanding what role brain glycogen plays in maintaining normal brain function,” says Rolf Gruetter of the University of Minnesota at Minneapolis St. Paul. His team studies brain glycogen in rats stressed by low concentrations of blood sugar. The group’s results suggest that brain-glycogen reserves are critical to survival. Like Geiger’s team, Gruetter’s group has found that the brain tends to overstock glycogen following stress.

“I’m excited that the glycogen hypothesis is continuing to receive attention,” says H. Craig Heller of Stanford University, a coauthor of the hypothesis that brain-energy stores control sleep. “I’m encouraged that our original idea held.”

However, the story is complex, Heller cautions. In an experiment similar to Geiger’s, Heller’s team failed to see brain-glycogen changes from sleep deprivation in the cortex of rats’ brains, one of the areas where Geiger’s team reported a large change. The finding appears in the July American Journal of Physiology–Regulatory, Integrative, and Comparative Physiology.

The results don’t necessarily conflict, Heller says, because his group used weaker microwaves and younger animals than Geiger’s team did. Also, glycogen depletion may vary from one brain area to another according to an animal’s circumstances, says Heller. For example, the part that controls a rat’s movements may become depleted if the animal is kept awake by physical activity, whereas sensory brain centers may become depleted if an animal is kept awake by loud noises or flashing lights.

Heller concludes, “It’s a continuing story, and this is just the beginning.”

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