Effects of centrally administered etanercept on behavior, microglia, and astrocytes in mice following a peripheral immune challenge

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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.date.issued2015
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.identifier.citationNeuropsychopharmacology, 2015; 40(2):502-512
dc.identifier.doi10.1038/npp.2014.199
dc.identifier.issn0893-133X
dc.identifier.issn1740-634X
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]
dc.identifier.urihttp://hdl.handle.net/2440/97746
dc.language.isoen
dc.publisherNature Publishing Group
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1003788
dc.rights© 2015 American College of Neuropsychopharmacology. All rights reserved.
dc.source.urihttps://doi.org/10.1038/npp.2014.199
dc.subjectHippocampus
dc.titleEffects of centrally administered etanercept on behavior, microglia, and astrocytes in mice following a peripheral immune challenge
dc.typeJournal article
pubs.publication-statusPublished

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