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Physiol. Genomics (August 14, 2007). doi:10.1152/physiolgenomics.00275.2006
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Submitted on December 13, 2006
Accepted on August 1, 2007

Macromolecule biosynthesis - a key function of sleep

Miroslaw Mackiewicz1*, Keith R Shockley2, Micah A Romer3, Raymond J. Galante3, John E Zimmerman4, Nirinjini Naidoo1, Donald A. Baldwin5, Shane T Jensen6, Gary A. Churchill2, and Allan I Pack1

1 Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States
2 The Jackson Laboratory, Bar Harbor, Maine, United States
3 Center for Sleep and Respiratory Neurobiology, University of Pennsylvania, Philadelphia, Pennsylvania, United States
4 Center for Sleep and Respiratory Neurobiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, United States
5 Penn Microarray Facility, University of Pennsylvania, Philadelphia, Pennsylvania, United States
6 Wharton School, University of Pennsylvania, Philadelphia, Pennsylvania, United States

* To whom correspondence should be addressed. E-mail: mirekmm{at}mail.med.upenn.edu.

The function(s) of sleep remains a major unanswered question in biology. We assessed changes in gene expression in the mouse cerebral cortex and hypothalamus following different durations of sleep and periods of sleep deprivation. There were significant differences in gene expression between behavioral states; we identified 3,988 genes in the cerebral cortex and 823 genes in the hypothalamus with altered expression patterns between sleep and sleep deprivation. Changes in the steady-state level of transcripts for various genes are remarkably common during sleep, as 2,090 genes in the cerebral cortex and 409 genes in the hypothalamus were defined as sleep-specific and changed (increased or decreased) their expression during sleep. The largest classes of over-represented genes increasing expression with sleep were those involved in biosynthesis and transport. In both the cerebral cortex and hypothalamus, there was up-regulation during sleep of multiple genes encoding various enzymes involved in cholesterol synthesis, as well as proteins for lipid transport. There was also up-regulation during sleep of genes involved in synthesis of proteins, heme, and maintenance of vesicle pools, as well as antioxidant enzymes and genes encoding proteins of energy-regulating pathways. We postulate that during sleep there is a rebuilding of multiple key cellular components in preparation for subsequent wakefulness.




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