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Effects of Centrally Administered Etanercept on Behavior, Microglia, and Astrocytes in Mice Following a Peripheral Immune Challenge.
- Source :
- Neuropsychopharmacology; Jan2015, Vol. 40 Issue 2, p502-512, 11p, 1 Chart, 6 Graphs
- Publication Year :
- 2015
-
Abstract
- Peripheral 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<subscript>(1,30)</subscript>=0.60, P=0.44; Saline/LPS challenge: F<subscript>(1,30)</subscript>=23.92, P<0.0001, etanercept vs aCSF: F<subscript>(1,30)</subscript>=11.09, P=0.0023). For cognition, a significant interaction effect found by two-way ANOVA (Interaction: F<subscript>(1,20)</subscript>=4.96, P=0.037, Saline/LPS challenge: F<subscript>(1,20)</subscript>=4.966, P=0.31, aCSF/etanercept treatment: F<subscript>(1,20)</subscript>=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<subscript>(1,15)</subscript>=11.41, P=0.0041; Saline/LPS challenge: F<subscript>(1,15)</subscript>=50.13, P<0.0001, etanercept vs aCSF: F<subscript>(1,15)</subscript>=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. [ABSTRACT FROM AUTHOR]
- Subjects :
- CYTOKINES
CENTRAL nervous system
NERVOUS system
NECROSIS
ASTROCYTES
Subjects
Details
- Language :
- English
- ISSN :
- 0893133X
- Volume :
- 40
- Issue :
- 2
- Database :
- Complementary Index
- Journal :
- Neuropsychopharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 99901303
- Full Text :
- https://doi.org/10.1038/npp.2014.199