Stress-induced anxiety is dependent upon caspase-1 processing of active IL-1β in brain macrophages

Loading...
Thumbnail Image

Date

2015-05

Journal Title

Journal ISSN

Volume Title

Publisher

The Ohio State University

Research Projects

Organizational Units

Journal Issue

Abstract

The murine repeated social defeat (RSD) model reveals that neuroimmune signaling is implicated in the development of stress-induced anxiety-like behavior. Work from our lab showed that the anxiety-like behavior exhibited following RSD is associated with microglial activation, increased recruitment of brain-macrophages, and increased IL-1b expression in the brain. Moreover, this neuroinflammatory process was dependent upon IL-1 receptor 1 in the CNS. To determine the source of cytokine production following stress, NanoString mRNA analysis was conducted on FACS-sorted microglia and brain-macrophages. This revealed that brain macrophages rather than resident microglia are the primary source of increased IL-1b mRNA production in the brain following repeated social defeat. To address the functional role of IL-1b in the development of anxiety-like behavior, caspase-1 knockout (KO) mice were used. Caspase-1 is required for the cleavage of pro-IL-1b into its active form. Results show that caspase-1 KO mice did not develop anxiety-like behavior following RSD. Furthermore, our data indicates that caspase-1 KO mice do not exhibit increased microglial activation as characterized by Iba-1 immunolabeling. However, caspase-1 KO mice still had increased peripheral macrophage trafficking to the brain and increased IL-1b mRNA expression in the brain. We interpret these results to indicate that the development of anxiety-like behavior is dependent on functional IL-1b released by brain macrophages that is cleaved by caspase-1.

Description

Keywords

Microglia, Neuroinflammation, Psychological Stress, Caspase-1, IL-1b

Citation