Adverse Effects of Circadian Disorganization on Mood and Molecular Rhythms in the Prefrontal Cortex of Mice

•Exposure to a disrupted light–dark cycle alters mood-related behaviors in mice.•Clock genes are abundantly expressed in the prefrontal cortex of mice.•Circadian disorganization alters rhythmic expression of clock and immediate early genes in the prefrontal cortex of mice.•The prefrontal cortex may play an important role in the integration of mood and the circadian clock. Disturbance of the daily cycles in sleep and wakefulness induced by conditions such as shift work and jet lag can increase the risk of affective disorders including anxiety and depression. The way such circadian disorganization disrupts the regulation of mood, however, is not well understood. More specifically, the impact of circadian disorganization on the daily rhythms of the neuronal function that controls mood remains unclear. We therefore investigated the effects of circadian disorganization on expression rhythms of clock genes as well as immediate early genes (IEGs) in several mood-controlling regions of the brain. To introduce circadian disorganization of behaviors, we exposed male C57BL/6J mice to chronic reversal of the light–dark cycle and we found a marked negative mood phenotype in these mice. Importantly, the most adverse effect of circadian disorganization on expression rhythms of clock and IEGs was observed in the prefrontal cortex (PFC) when compared to that in other mood-related areas of the brain. Dysregulation of molecular rhythms in the PFC is therefore suggested to be associated with the development of mood disorders in conditions including shift work and jet lag.