Pluto Bioinformatics

GSE149195: Sequencing to determine the effect of neuronal IL-1b receptor knockout on the stress effect of paired fighting social defeat in mice

Bulk RNA sequencing

Chronic stress contributes to the development of psychiatric disorders including anxiety and depression. Several inflammatory-related effects of stress are associated with increased interleukin-1 (IL-1) signaling within the central nervous system and are mediated by IL-1 receptor 1 (IL-1R1) on several distinct cell types. Neuronal IL-1R1 is prominently expressed on the neurons of the dentate gyrus, but its role in mediating behavioral responses to stress is unknown. We hypothesize that IL-1 acts on this subset of hippocampal neurons to influence cognitive and mood alterations with stress. Here, mice subjected to psychosocial stress showed reduced social interaction and impaired working memory, and these deficits were prevented by global IL-1R1 knockout. Selective deletion of IL-1R1 in glutamatergic neurons (nIL-1R1-/-), abundant in the hippocampus wherein the inflammatory-influenced effects were observed, abrogated the stress-induced deficits in social interaction and working memory. RNA-sequencing of microdissected hippocampi revealed that stress increased several canonical pathways (TREM1, NF-, complement, IL-6 signaling) and upstream regulators (INF, IL-1, NF-B, MYD88) associated with inflammation. The inductions of TREM1 signaling, complement, and leukocyte extravasation with stress were reversed by nIL-1R1-/-. Collectively, we show that stress-dependent IL-1R1 signaling in hippocampal neurons represents a novel mechanism by which inflammation is perpetuated and social interactivity and working memory are modulated. SOURCE: Damon,Joseph,DiSabato The Ohio State University