Nighttime-specific gene expression changes in suprachiasmatic nucleus and habenula are associated with resiliency to chronic social stress

Mood disorder is bidirectionally associated with the dysregulation of circadian rhythms and sleep/wake cycle. However, the molecular mechanisms that link these processes remain largely unclear. The habenula (Hb) is a key brain region involved in mood regulation and depression, while the suprachiasmatic nucleus (SCN) is the body's central clock. We investigated the effects of chronic social defeat stress (CSDS) on gene expression in the Hb and SCN of stress-resilient and susceptible mice. Bulk RNA-seq analysis was conducted across four timepoints throughout the day, including the middle of the inactive (daytime) and active (nighttime) phases as well as during the transition periods. Differential expression analysis revealed a large number of differentially expressed genes and strong pathway activation in the resilient mice at ZT16 in both the Hb and SCN. This effect was timepoint and phenotype-specific. Our results reinforce the functional link between diurnal expression patterns and differential responses to stress. Specifically, we show potentially novel molecular mechanisms at night in the Hb and SCN that are associated with resilience to stress. ### Competing Interest Statement The authors have declared no competing interest.