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dc.contributor.authorCamara, M.-
dc.contributor.authorCorrigan, F.-
dc.contributor.authorJaehne, E.-
dc.contributor.authorJawahar, M.-
dc.contributor.authorAnscomb, H.-
dc.contributor.authorBaune, B.-
dc.identifier.citationNeuropsychopharmacology, 2015; 40(2):502-512-
dc.descriptionPublished online 17 September 2014-
dc.description.abstractPeripheral cytokines affect central nervous system (CNS) function, manifesting in symptoms of anxiety and cognitive decline. Although the peripheral blockage of tumor necrosis factor (TNF)-α has been effective in alleviating depression and rheumatoid arthritis, it is yet unknown whether central blockade of TNF-α is beneficial for immune-challenged CNS function. This study investigated the effects of central etanercept administration following a peripheral immune challenge on anxiety-like and cognition-like behaviors and microglia and astrocyte numbers. Twelve-week-old C57BL/6 mice (n=40) were treated with either LPS or saline administered peripherally 24 h before being treated with either etanercept or artificial CSF (aCSF) by intracerebroventricular injection. Mice underwent behavioral analyses for locomotion, memory, and anxiety-like behavior 24 h post-etanercept/aCSF treatment, and tissue was collected to estimate the numbers of hippocampal microglia and astrocytes. Following peripheral immune challenge with LPS, mice showed increased anxiety-like behavior, which was significantly improved following treatment with etanercept (two-way ANOVA: Interaction: F(1,30)=0.60, P=0.44; Saline/LPS challenge: F(1,30)=23.92, P<0.0001, etanercept vs aCSF: F(1,30)=11.09, P=0.0023). For cognition, a significant interaction effect found by two-way ANOVA (Interaction: F(1,20)=4.96, P=0.037, Saline/LPS challenge: F(1,20)=4.966, P=0.31, aCSF/etanercept treatment: F(1,20)=0.06, P=0.80) and post-hoc analysis revealed a significant decrease in cognition in LPS-aCSF compared with Sal-aCSF mice (P=0.038), but no significant difference was noted between LPS-aCSF and LPS-Etan mice (P>0.9). A significant reduction in the number of microglia within the hippocampus of these mice was noted (two-way ANOVA: Interaction: F(1,15)=11.41, P=0.0041; Saline/LPS challenge: F(1,15)=50.13, P<0.0001, etanercept vs aCSF: F(1,15)=3.36, P=0.08). Centrally administered etanercept improved anxiety-like behavior but not spatial memory under a peripheral immune challenge and was associated with a decrease in the hippocampal microglia numbers. This suggests that etanercept recovers anxiety-like behavior possibly mediated by a reduction of TNF-α-related central inflammation.-
dc.description.statementofresponsibilityMarie lou Camara, Frances Corrigan, Emily J Jaehne, Magdalene C Jawahar, Helen Anscomb and Bernhard T Baune-
dc.publisherNature Publishing Group-
dc.rights© 2015 American College of Neuropsychopharmacology. All rights reserved.-
dc.titleEffects of centrally administered etanercept on behavior, microglia, and astrocytes in mice following a peripheral immune challenge-
dc.typeJournal article-
dc.identifier.orcidCorrigan, F. [0000-0001-6150-8893]-
dc.identifier.orcidJaehne, E. [0000-0003-0532-1623]-
dc.identifier.orcidJawahar, M. [0000-0001-7136-1848]-
dc.identifier.orcidBaune, B. [0000-0001-6548-426X]-
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