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.

Public Health Relevance

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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH109165-02
Application #
9222049
Study Section
Pathophysiological Basis of Mental Disorders and Addictions Study Section (PMDA)
Program Officer
Winsky, Lois M
Project Start
2016-02-10
Project End
2020-11-30
Budget Start
2016-12-01
Budget End
2017-11-30
Support Year
2
Fiscal Year
2017
Total Cost
Indirect Cost
Name
Ohio State University
Department
Dentistry
Type
Schools of Dentistry/Oral Hygn
DUNS #
832127323
City
Columbus
State
OH
Country
United States
Zip Code
43210
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
Liu, Xiaoyu; Quan, Ning (2018) Microglia and CNS Interleukin-1: Beyond Immunological Concepts. Front Neurol 9:8