DiffBrainNet: A combined resource of differential networks and differential expression to analyze transcriptomic responses to glucocorticoids in 8 mouse brain regions.

Activation of the stress-axis is an important component of the biology of stress-related psychiatric disorders. The main stress hormones of the mammalian body are glucocorticoids. Glucocorticoids bind to glucocorticoid receptors and act as transcription factors modulating the transcriptional landscape. Dexamethasone is a synthetic glucocorticoid that is used to activate the glucocorticoid receptors and thus mimic some aspects of the altered transcriptomic landscape that are associated with stress-related psychiatric disorders. We used intraperitoneal dexamethasone of C57Bl/6 mice and analyzed the transcriptional landscape of 8 brain regions: the prefrontal cortex, the amygdala, the paraventricular nucleus of the hypothalamus, the dorsal and ventral Cornu ammonis 1, the dorsal and ventral dentate gyrus and the cerebellar cortex. We implored differential expression in combination with differential network analysis to study the transcriptomic responses to dexamethasone in each brain region. We found that differential networks and differential expression explain distinct but complementary aspects of the responses to the stimulus and that network analysis can unravel underlying biological mechanisms that are hidden at the gene level. Using our dataset we could analyze the molecular connectivity of Tcf4, an important psychiatric risk gene, at the baseline and differential levels. We provide an analysis framework and a resource for the study of the transcriptional landscape of 8 mouse brain regions at baseline, dexamethasone-treated and differential levels, called DiffBrainNet (http://134.76.24.68/app/diffbrainnet), that can be used pinpoint molecular pathways important for the basic functioning and response to glucocorticoids in a brain-region specific manner. RNA sequencing with subsequent differential expression analysis an differential network analysis in 8 brain regions (PFC, PVN, AMY, vDG, dDG, vCA1, dCA1, CER) after dexamethasone treatment (IP, 10mg/kg, 4 hours) of adult male C57Bl/6 mice (15 controls and 15 dexamethasone treated).