Role of the NLRP3 inflammasome in stress-induced neuroinflammation and anxiety-like behavior
Loading...
Date
2017-12
Authors
Sobol, Carly G.
Journal Title
Journal ISSN
Volume Title
Publisher
The Ohio State University
Abstract
Exposure to chronic stress or traumatic events increases the risk of developing mood or anxiety disorders (1). In conjunction, mounting evidence indicates that neuroinflammation is linked with the etiology of psychiatric disorders, including depression and anxiety (2). Specifically, pro-inflammatory cytokines, such as IL-1β, mediate changes to mood, cognition, and behavior that closely resemble characteristics observed in mood and anxiety disorders (3). Therefore, stress may increase vulnerability towards psychiatric disorders by enhancing neuroinflammatory processes. In support of this, our laboratory uses the repeated social defeat (RSD) murine stress model to measure the effects of stress on neuroinflammation and behavior. We have previously demonstrated that exposure to RSD stimulates monocyte trafficking from the bone marrow to fear and threat appraisal centers of the brain (4). This finding is significant because the monocyte population that traffics to the brain highly expresses IL-1β and propagates neuroinflammation that is associated with the development of anxiety-like behavior (5). We hypothesize that IL-1β is a key signaling molecule for the neuroinflammatory and behavioral effects of stress exposure. However, the role of IL-1β in these processes is unknown.
IL-1β is a pro-inflammatory cytokine that is expressed by activated macrophages and microglia, and causes inflammation in the CNS that promotes anxiety/ depressive like behaviors observed after stress (RSD) (6). IL-1β is released after cleavage from a proprotein form (proIL- 1β) by the enzyme caspase-1 (7). Similarly, Caspase-1 is activated following cleavage from pro- Caspase-1 by the NLRP3 inflammasome. Thus, the NLRP3 inflammasome is a critical step for
IL-1β to be released. Therefore, knocking out the NLRP3 gene is expected to prevent the release of IL-1β, which we hypothesize to inhibit depressive/anxiety-like behavior in response to RSD. This study will provide insight into the role of the NLRP3 inflammasome and allow further research into uncovering the cellular mechanistic immunological pathway responsible for stress- induced anxiety/depression.
Description
Keywords
anxiety, inflammation, inflammasome, stress