Changes in brain gene expression after long‐term sleep deprivation

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Abstract
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, α‐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.