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Knockdown of Interleukin-1 Receptor Type-1 on Endothelial Cells Attenuated Stress-Induced Neuroinflammation and Prevented Anxiety-Like Behavior
Open accessAbstract
Interleukin-1β (IL-1β) is an inflammatory cytokine that plays a prominent role in stress-induced behavioral changes. In a model of repeated social defeat (RSD), elevated IL-1β expression in the brain was associated with recruitment of primed macrophages that were necessary for development of anxiety-like behavior. Moreover, microglia activation and anxiety-like behavior associated with RSD did not occur in IL-1 receptor type-1 knock-out (IL-1R1 KO) mice. Therefore, the objective of this study was to examine the role of IL-1 signaling in RSD-induced macrophage trafficking to the brain and anxiety-like behavior. Initial studies revealed that RSD did not increase circulating myeloid cells in IL-1R1 KO mice, resulting in limited macrophage trafficking to the brain. In addition, IL-1R1 KO bone marrow-chimera mice showed that IL-1R1 expression was essential for macrophage trafficking into the brain. To differentiate cellular mediators of stress-induced IL-1 signaling, endothelial-specific IL-1R1 knock-down (eIL-1R1kd) mice were used. Both wild-type (WT) and eIL-1R1kd mice had increased circulating monocytes, recruitment of macrophages to the brain, and altered microglia activation after RSD. Nonetheless, RSD-induced expression of IL-1β, TNF-α, and IL-6 mRNA in brain CD11b+cells was attenuated in eIL-1R1kd mice compared with WT. Moreover, anxiety-like behavior did not develop in eIL-1R1kd mice. Collectively, these findings demonstrated that there was limited RSD-induced priming of myeloid cells in IL-1R1 KO mice and disrupted propagation of neuroinflammatory signals in the brain of eIL-1R1kd mice. Furthermore, these data showed that transduction of IL-1 signaling by endothelial cells potentiates stress-induced neuroinflammation and promotes anxiety-like behavior.
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“Stress- induced redistribution of myeloid cells to the spleen leads to long-term immune and behavioral sensitization to subthreshold stressors.”
From Repeated Social Defeat, Neuroinflammation, and Behavior: Monocytes Carry the Signal (2017) · cites this paper as [141]
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Metadata
- Authors
- Wohleb, E. S., Patterson, J. M., Sharma, V., Quan, N., Godbout, J. P., & Sheridan, J. F.
- Affiliations
- The Ohio State University (US)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2014-02-12
- Volume
- 34
- Issue
- 7
- Pages
- 2583-2591
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC3921428
- OpenAlex
- W2070447896
- Cited by
- 209
- References
- 50
- Citations by year
- 2026: 10 · 2025: 8 · 2024: 15 · 2023: 20 · 2022: 17 · 2021: 18 · 2020: 16 · 2019: 24 · 2018: 14 · 2017: 20 · 2016: 19 · 2015: 15 · 2014: 11
- FWCI
- 11.25
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (1f31mh095473-01a1)
- National Institute on Aging (R01AG033028)
- National Institute of Mental Health (R01MH097243, F31-MH09547301, R01MH093473)
- 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
- IL1R1, interleukin-1β signaling, endothelial cells, anxiety-like behavior, repeated social defeat, microglial activation, myeloid cells, bone marrow chimeras, TNF-α, interleukin-6
- MeSH terms
- Animals, Anxiety, Behavior, Animal, Brain, Chemotaxis, Leukocyte, Flow Cytometry, Fluorescent Antibody Technique, Interleukin-1, Macrophages, Male, Mice, Inbred C57BL, Stress, Psychological, Signal Transduction, Mice, Knockout, Endothelial Cells, Mice, Receptors, Interleukin-1 Type I, Real-Time Polymerase Chain Reaction
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