Anxiety, IL-1R1 and neuroinflammation

 描述(由申请人提供)：越来越多的证据表明，炎症是包括抑郁和焦虑在内的精神病理的致病因素。我们合作小组的工作已经证实，炎症细胞因子白介素1(IL-1)是应激诱导焦虑的关键介质。然而，IL-1诱导炎性焦虑的途径仍不清楚。在R01的应用中，我们将研究新的假设，即IL-1作用于脑内皮细胞，触发炎性小胶质细胞激活，这是诱导焦虑行为所必需的。我们将使用我们新创建的IL-1R1恢复小鼠系来研究特定细胞类型的IL-1R1介导的小胶质细胞激活，并分离IL-1参与焦虑症的致病途径。

 DESCRIPTION (provided by applicant): 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.