Changes in brain gene expression after long-term sleep deprivation.
Long-term sleep deprivation in rats produces dramatic physiological changes including increase in energy expenditure, decrease in body weight, and death after 2-3 weeks. Despite several studies, the sleep deprivation syndrome remains largely unexplained. Here, to elucidate how prolonged sleep loss affects brain cells we used microarrays and screened the expression of > 26 000 transcripts in the cerebral cortex. Rats were sleep deprived using the disk-over-water method for 1 week. Seventy-five transcripts showed increased expression in these animals relative to controls that had been spontaneously awake or sleep deprived for a few hours. Most of them were induced as a result of chronic sleep loss and not non-specific effects of the disk stimulation. They include transcripts coding for several immunoglobulins, stress response proteins (macrophage inhibitor factor-related protein 14, heat-shock protein 27, alpha-B-crystallin), minoxidil sulfotransferase, globins and cortistatin. Twenty-eight transcripts decreased their expression in long-term sleep-deprived rats. Sixteen of them were specifically decreased as a result of chronic sleep loss, including those coding for type I procollagen and dihydrolipoamide acetyltransferase. We also compared sleeping rats to short-term and long-term sleep-deprived rats, and found that acute and chronic sleep loss led to some differences at the molecular level. Several plasticity-related genes were strongly induced after acute sleep deprivation only, and several glial genes were down-regulated in both sleep deprivation conditions, but to a different extent. These findings suggest that sustained sleep loss may trigger a generalized inflammatory and stress response in the brain.
Cirelli
Chiara
C
Department of Psychiatry, University of Wisconsin, Madison, Wisconsin 53719, USA. ccirelli@wisc.edu
Faraguna
Ugo
U
Tononi
Giulio
G
D000818:Animals; D001522:Behavior, Animal; D001921:Brain / Q000503:physiopathology*; D004569:Electroencephalography / Q000379:methods; D015870:Gene Expression / Q000502:physiology*; D005786:Gene Expression Regulation / Q000502:physiology*; D008297:Male; D046228:Microarray Analysis / Q000379:methods; D051381:Rats; D011921:Rats, Inbred WKY; D012892:Sleep Deprivation / Q000503:physiopathology*; D013997:Time Factors; D014851:Wakefulness / Q000502:physiology