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Physiol. Genomics 31: 441-457, 2007. First published August 14, 2007; doi:10.1152/physiolgenomics.00275.2006
1094-8341/07 $8.00
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Received 13 December 2006; accepted in final form 1 August 2007.
Physiological Genomics 31:441-457 (2007)
1094-8341/06 $8.00 © 2007 American Physiological Society

Macromolecule biosynthesis: a key function of sleep

Miroslaw Mackiewicz 1,2, Keith R. Shockley 3, Micah A. Romer 1, Raymond J. Galante 1, John E. Zimmerman 1, Nirinjini Naidoo 1,2, Donald A. Baldwin 4, Shane T. Jensen 5, Gary A. Churchill 3 and Allan I. Pack 1,2

1 Center for Sleep and Respiratory Neurobiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania
2 Division of Sleep Medicine/Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania
3 The Jackson Laboratory, Bar Harbor, Maine
4 University of Pennsylvania Microarray Facility, University of Pennsylvania, Philadelphia, Pennsylvania
5 The Wharton School, University of Pennsylvania, Philadelphia, Pennsylvania

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 categories of overrepresented genes increasing expression with sleep were those involved in biosynthesis and transport. In both the cerebral cortex and hypothalamus, during sleep there was upregulation of multiple genes encoding various enzymes involved in cholesterol synthesis, as well as proteins for lipid transport. There was also upregulation 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.

gene expression; microarray; cholesterol; protein synthesis




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