185 Repeated Social Defeat Induces Recruitment of Macrophages to the CNS

Thursday, March 22, 2012: 10:45 a.m. - 12:15 p.m.
Presentation Type: Oral Session
E.S. WOHLEB1, N.D. POWELL2, J.P. GODBOUT1, and J.F. SHERIDAN2, 1Neuroscience, Ohio State University, Columbus, OH, 2College of Dentistry, Ohio State University, Columbus, OH
Objective: Psychosocial stress has a profound impact on physiology, behavior, and immunity. Previous studies showed that repeated social defeat (RSD) enhanced the trafficking capacity and inflammatory responses of peripheral and brain CD11b+ cells. In addition, RSD increased the number of inflammatory macrophages (CD11b+/CD45high) associated with the brain. The objective of this study was to determine the location of peripheral CD11b+ cells and role of IL-1 signaling in recruitment of these cells to the central nervous system (CNS) following RSD.

Methods: To examine recruitment of peripheral CD11b+ cells to the brain we developed GFP+ bone marrow (BM) chimeric mouse and exposed these mice to RSD. In the first study enriched CD11b+ cells were isolated from whole brains and GFP+ cells were analyzed using flow cytometry. To establish the location of GFP+ cells a subset of mice were perfused and brains were used for histological analyses. In the second study we exposed IL-1 receptor type-1 deficient (IL-1r1-/-) mice to RSD and enriched brain CD11b+ cells were collected to analyze cellular phenotypes. In addition, GFP+ BM-derived cells from wild-type mice were transferred into IL-1r1-/- mice. Following RSD these IL-1r1-/- chimeric mice were perfused and brains were used for histological analyses.

Results: RSD increased the number of GFP+ cells associated with the brain and these GFP+ cells were predominantly CD11b+ (>85%). GFP+/CD11b+ cells exhibited an inflammatory profile through higher expression of Ly6C. Brains obtained from RSD mice revealed that GFP+ cells were localized in specific stress-responsive brain regions. The GFP+ cells co-localized with Iba-1 immunofluorescence indicating that these cells were derived from a myeloid lineage. Furthermore, the presence of GFP+ cells was absent in the brains of IL-1r1-/- chimeric mice.

Conclusions: RSD induced recruitment of macrophages (CD11b+/Ly6Chigh) to specific regions in the CNS and this was dependent on systemic expression of IL-1r1.

This abstract is based on research that was funded entirely or partially by an outside source: NIA grant R01-AG033028-02; NIDCR grant (CTOC) T32-DE-01-4320

Keywords: Central nervous system/peripheral nervous system, Immunology, Inflammation, Neuroscience and Stress
See more of: Neuroscience I
See more of: Neuroscience
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