Cited by 102Neuroinflammation and Neurodegeneration MechanismsTryptophan and brain disordersStress Responses and Cortisol

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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

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Sawicki, C.M., McKim, D.B., Wohleb, E.S., Jarrett, B.L., Reader, B.F., Norden, D.M., Godbout, J.P., Sheridan, J.F.·2015·Neuroscience

DOI 10.1016/j.neuroscience.2014.10.004PMC PMC4397120

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Abstract

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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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.
ORCID: Sawicki, C.M.
McKim, D.B.
Wohleb, E.S.
Reader, B.F.
Godbout, J.P.
Sheridan, J.F.
Venue: Neuroscience
Publisher: Elsevier BV
Published: 2015-08
Volume: 302
Pages: 151-164
ISSN: 0306-4522 (ISSN-L)
DOI: 10.1016/j.neuroscience.2014.10.004
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
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
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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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

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