Diurnally regulated gene expression in the prefrontal cortex of C57Bl/6J mice at Zeitgeber Time (ZT) 3, 9, 15, and 21.

Background: The prefrontal cortex is important in regulating sleep and mood. Diurnally regulated genes in the prefrontal cortex may be controlled by the circadian system, by the sleep-wake states, or by cellular metabolism or environmental responses. Bioinformatics analysis of these genes will provide insights into a wide-range of pathways that are involved in the pathophysiology of sleep disorders and psychiatric disorders with sleep disturbances. Results: We examined gene expression in the mouse prefrontal cortex at four time points during the 24-hour (12-hour light:12-hour dark) cycle by microarrays, and identified 3,890 transcripts corresponding to 2,927 genes with diurnally regulated expression patterns. We show that 16% of the genes identified in our study are orthologs of identified clock, clock controlled or sleep/wakefulness induced genes in the mouse liver and SCN, rat cortex and cerebellum, or Drosophila head. The diurnal expression patterns were confirmed in 16 out of 18 genes in an independent set of RNA samples. The diurnal genes fall into eight temporal categories with distinct functional attributes, as assessed by the Gene Ontology classification and by the analysis of enriched transcription factor binding sites. Conclusions: Our analysis demonstrates that ~10% of transcripts have diurnally regulated expression patterns in the mouse prefrontal cortex. Functional annotation of these genes will be important for the selection of candidate genes for behavioural mutants in the mouse and for genetic studies of disorders associated with anomalies in the sleep:wake cycle and circadian rhythms.

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Yang S, Wang K, Valladares O, Hannenhalli S, Bucan M