Increasing evidence points to inflammation as contributing factor for the pathogenesis of psychopathologies, including depression and anxiety. Work from our collaborative group has established that the inflammatory cytokine interleukin-1 (IL-1) is a crucial mediator of stress induced anxiety. The pathways by which IL-1 induces inflammatory anxiogenesis, however, remain unknown. In this R01 application, we will investigate the novel hypothesis that IL-1 acts on brain endothelial cells to trigger inflammatory microglial activation, which is required for the induction of anxiety behaviors. We will use our newly created IL-1R1 restore mouse lines to study cell type specific IL-1R1 mediated microglial activation and isolate the pathogenic pathways by which IL-1 contributes to anxiogenesis.
for 'Anxiety, IL-1R1 and neuroinflammation'. This study investigates the pathway by which inflammatory processes contribute to anxiogenesis. We will use a newly created powerful genetic model to elucidate IL-1 mediated signaling events that contribute to the pathogenesis of anxiety disorders.
|Liu, Xiaoyu; Quan, Ning (2018) Microglia and CNS Interleukin-1: Beyond Immunological Concepts. Front Neurol 9:8|
|Song, Anping; Zhu, Ling; Gorantla, Gowthami et al. (2018) Salient type 1 interleukin 1 receptor expression in peripheral non-immune cells. Sci Rep 8:723|
|McKim, D B; Weber, M D; Niraula, A et al. (2018) Microglial recruitment of IL-1?-producing monocytes to brain endothelium causes stress-induced anxiety. Mol Psychiatry 23:1421-1431|