Differences in brain gene expression between sleep and waking as revealed by mRNA differential display and cDNA microarray technology

The consequences of sleep and sleep deprivation at the molecular level are largely unexplored. Knowledge of such molecular events is essential to unde rstand the restorative processes occurring during sleep as well as the cell ular mechanisms of sleep regulation. Here we review the available data abou t changes in neural gene expression across different behavioural states usi ng candidate gene approaches such as in situ hybridization and immunocytoch emistry. We then describe new techniques for systematic screening of gene e xpression in the brain, such as subtractive hybridization, mRNA differentia l display, and cDNA microarray technology, outlining advantages and disadva ntages of these methods. Finally, we summarize our initial results of a sys tematic screening of gene expression in the rat brain across behavioural st ates using mRNA differential display and cDNA microarray technology. The ex pression pattern of approximate to 7000 genes was analysed in the cerebral cortex of rats after 3 h of spontaneous sleep, 3 h of spontaneous waking, o r 3 h of sleep deprivation. While the majority of transcripts were expresse d at the same level among these three conditions, 14 mRNAs were modulated b y sleep and waking. Six transcripts, four more expressed in waking and two more expressed in sleep, corresponded to novel genes. The eight known trans cripts were all expressed at higher levels in waking than in sleep and incl uded transcription factors and mitochondrial genes. A possible role for the se known transcripts in mediating neural plasticity during waking is discus sed.