| First Author | Wohleb ES | Year | 2014 |
| Journal | J Neurosci | Volume | 34 |
| Issue | 7 | Pages | 2583-91 |
| PubMed ID | 24523548 | Mgi Jnum | J:206939 |
| Mgi Id | MGI:5553388 | Doi | 10.1523/JNEUROSCI.3723-13.2014 |
| Citation | Wohleb ES, et al. (2014) Knockdown of interleukin-1 receptor type-1 on endothelial cells attenuated stress-induced neuroinflammation and prevented anxiety-like behavior. J Neurosci 34(7):2583-91 |
| abstractText | Interleukin-1beta (IL-1beta) is an inflammatory cytokine that plays a prominent role in stress-induced behavioral changes. In a model of repeated social defeat (RSD), elevated IL-1beta 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-1beta, TNF-alpha, 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. |
