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Social defeat promotes a reactive endothelium in a brain region-dependent manner with increased expression of key adhesion molecules, selectins and chemokines associated with the recruitment of myeloid cells to the brain
Open accessAbstract
Repeated social defeat (RSD) in mice causes myeloid cell trafficking to the brain that contributes to the development of prolonged anxiety-like behavior. Myeloid cell recruitment following RSD occurs in regions where neuronal and microglia activation is observed. Thus, we hypothesized that crosstalk between neurons, microglia, and endothelial cells contributes to brain myeloid cell trafficking via chemokine signaling and vascular adhesion molecules. Here we show that social defeat caused an exposure- and brain region-dependent increase in several key adhesion molecules and chemokines involved in the recruitment of myeloid cells. For example, RSD induced distinct patterns of adhesion molecule expression that may explain brain region-dependent myeloid cell trafficking. VCAM-1 and ICAM-1 mRNA expression were increased in an exposure-dependent manner. Furthermore, RSD-induced VCAM-1 and ICAM-1 protein expression were localized to the vasculature of brain regions implicated in fear and anxiety responses, which spatially corresponded to previously reported patterns of myeloid cell trafficking. Next, mRNA expression of additional adhesion molecules (E- and P-selectin, PECAM-1) and chemokines (CXCL1, CXCL2, CXCL12, CCL2) were determined in the brain. Social defeat induced an exposure-dependent increase in mRNA levels of E-selectin, CXCL1, and CXCL2 that increased with additional days of social defeat. While CXCL12 was unaffected by RSD, CCL2 expression was increased by six days of social defeat. Last, comparison between enriched CD11b(+) cells (microglia/macrophages) and enriched GLAST-1(+)/CD11b(-) cells (astrocytes) revealed RSD increased mRNA expression of IL-1β, CCL2, and CXCL2 in microglia/macrophages but not in astrocytes. Collectively, these data indicate that key mediators of leukocyte recruitment were increased in the brain vasculature following RSD in an exposure- and brain region-dependent manner.
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“Repeated social defeat induces cell adhesion molecule (ICAM-1, VCAM, E-Selectin) and IL-1 receptor-1 expression on the brain vasculature that provide interaction sites for monocytes recruited from the periphery [17, 21, 35].”
From Interleukin-6 Induced by Social Stress Promotes a Unique Transcriptional Signature in the Monocytes That Facilitate Anxiety (2019) · cites this paper as [35]
In the citing paper
“Both ICAM and VCAM were increased after 6 days of social defeat that temporally correlated with peripheral monocyte trafficking (Sawicki et al, 2015).”
From Repeated Social Defeat, Neuroinflammation, and Behavior: Monocytes Carry the Signal (2017) · cites this paper as Sawicki et al, 2015
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“Indeed, RSD increased expression of E-selectin selectively in stress-reactive brain regions where monocyte trafficking occurs (Sawicki et al, 2015).”
From Repeated Social Defeat, Neuroinflammation, and Behavior: Monocytes Carry the Signal (2017) · cites this paper as Sawicki et al, 2015
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Metadata
- Authors
- Sawicki, C. M., McKim, D. B., Wohleb, E. S., Jarrett, B. L., Reader, B. F., Norden, D. M., Godbout, J. P., & Sheridan, J. F.
- Affiliations
- The Ohio State University (US)
- Corresponding author
- Godbout, J.P.
- Sheridan, J.F.
- Venue
- Neuroscience
- Publisher
- Elsevier BV
- Published
- 2015-08
- Volume
- 302
- Pages
- 151-164
- ISSN
- 0306-4522 (ISSN-L)
- PMC
- PMC4397120
- OpenAlex
- W2005471473
- Cited by
- 101
- References
- 67
- Citations by year
- 2026: 5 · 2025: 7 · 2024: 11 · 2023: 11 · 2022: 10 · 2021: 9 · 2020: 7 · 2019: 10 · 2018: 11 · 2017: 3 · 2016: 10 · 2015: 6
- FWCI
- 3.29
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- NIMH (R01-MH-093473, R01-MH093472)
- NIDCR Training (T32-DE014320)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Keywords
- repeated social defeat, myeloid cell trafficking, brain endothelium, adhesion molecules, selectins, chemokines, VCAM-1, ICAM-1, E-selectin, CD31, microglia, astrocytes, anxiety-like behavior, leukocyte recruitment, neuroinflammation
- MeSH terms
- Analysis of Variance, Animals, Astrocytes, Brain, Disease Models, Animal, Endothelium, Gene Expression Regulation, Male, RNA, Messenger, Stress, Psychological, Cell Adhesion Molecules, Microglia, Chemokines, Selectins, Myeloid Cells, Mice
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