The Body Sleeps, but the Genes Do Not

FISHING IN THE DARK

The study, published in Neuron, was "a fishing expedition," acknowledges lead author Chiara Cirelli of the University of Wisconsin, Madison, "prompted by the desperation of not being able to understand what sleep is for." The authors used high-density microarrays to analyze brain-gene expression in awake, sleeping, and sleep-deprived rats.

Researchers have previously unearthed circadian genes differentially expressed during day and night. Cirelli's group found that for some of these, upregulation is attributable to sleep itself. The team found that of some 15,000 transcripts present in rat cerebral cortex, about 10% (1,564) were differentially expressed by day or night. But the group also found that for about half of these (752), the change was attributable to the waking or sleeping state, independent of time.

The authors focused on the cortex because it creates sleep's characteristic electrical rhythms, underlies cognitive defects tied to sleep deprivation, and is at the center of most hypotheses concerning sleep's functions. They also found that the cerebellum displays largely the same gene-expression sleep signature as the cerebrum, a key discovery, says Paul Shaw of Washington University School of Medicine, St. Louis.

Cerebellar involvement in sleep was hitherto unknown, because the structure doesn't participate in the sleep-related electrical oscillations characterizing other brain structures. The finding has "large phylogenetic implications," Shaw says. For instance, "The fruit fly doesn't have a cortex to generate these electrophysiological signatures. So this shows sleep is really a fundamental biological process."

Cirelli and colleagues also checked rat liver and skeletal muscle for upregulation of the sleep-related genes in the brain but found none. Increased translational machinery transcripts in the brain suggest that protein-synthesis increases during sleep.

Other so-called sleep genes found to influence membrane trafficking at various levels include those for exocytosis, neuro-transmitter release, synaptic vesicle recycling, and tethering and docking of vesicles to organelles. Still others code for membrane synthesis, especially myelin and one of its key components, cholesterol. The authors cite recent evidence that glia-derived cholesterol may be crucial for synapse formation and maintenance, which could, in turn, enhance neural plasticity (the brain's ability to change and learn). "The state of the membrane is going to influence whether a cell responds to the right signals," Shaw says, so "I'd be quite surprised if [these genes] didn't influence learning and memory."

Jack Lucentini jekluc@aol.com is a freelance writer in New York City.