Cytokines and chemokines as biomarkers of ethanol-induced neuroinflammation and anxiety-related behavior: Role of TLR4 and TLR2
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comunitat-uji-handle2:10234/8033
comunitat-uji-handle3:10234/8636
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http://dx.doi.org/10.1016/j.neuropharm.2014.10.014 |
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Title
Cytokines and chemokines as biomarkers of ethanol-induced neuroinflammation and anxiety-related behavior: Role of TLR4 and TLR2Date
2015Publisher
SpringerISSN
0028-3908; 1873-7064Bibliographic citation
PASCUAL, María, et al. Cytokines and chemokines as biomarkers of ethanol-induced neuroinflammation and anxiety-related behavior: role of TLR4 and TLR2. Neuropharmacology, 2015, vol. 89, p. 352-359.Type
info:eu-repo/semantics/articlePublisher version
http://www.sciencedirect.com/science/article/pii/S002839081400389XVersion
info:eu-repo/semantics/publishedVersionSubject
Abstract
Recent evidence supports the influence of neuroimmune system activation on behavior. We have demonstrated that ethanol activates the innate immune system by stimulating toll-like receptor 4 (TLR4) signaling in glial ... [+]
Recent evidence supports the influence of neuroimmune system activation on behavior. We have demonstrated that ethanol activates the innate immune system by stimulating toll-like receptor 4 (TLR4) signaling in glial cells, which triggers the release of inflammatory mediators and causes neuroinflammation. The present study aimed to evaluate whether the ethanol-induced up-regulation of cytokines and chemokines is associated with anxiety-related behavior, 24 h after ethanol removal, and if TLR4 or TLR2 is involved in these effects. We used WT, TLR4-KO and TLR2-KO mice treated with alcohol for 5 months to show that chronic ethanol consumption increases the levels of cytokines (IL-1β, IL-17, TNF-α) and chemokines (MCP-1, MIP-1α, CX3CL1) in the striatum and serum (MCP-1, MIP-1α, CX3CL1) of WT mice. Alcohol deprivation for 24 h induces IFN-γ levels in the striatum and maintains high levels of some cytokines (IL-1β, IL-17) and chemokines (MIP-1α, CX3CL1) in this brain region. The latter events were associated with an increase in anxiogenic-related behavior, as evaluated by the dark and light box and the elevated plus maze tests. Notably, mice lacking TLR4 or TLR2 receptors are largely protected against ethanol-induced cytokine and chemokine release, and behavioral associated effects during alcohol abstinence. These data support the role of TLR4 and TLR2 responses in neuroinflammation and in anxiogenic-related behavior effects during ethanol deprivation, and also provide evidence that chemokines and cytokines can be biomarkers of ethanol-induced neuroimmune response. [-]
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Neuropharmacology, 2015, vol. 89Rights
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