Exaggerated sickness behavior and brain proinflammatory cytokine expression in aged mice in response to intracerebroventricular lipopolysaccharide
Abstract
Age-associated changes in glial reactivity may predispose individuals to exacerbated neuroinflammatory cytokine responses that are permissive to cognitive and behavioral complications. The purpose of this study was to determine if aging is associated with an exaggerated sickness response to central innate immune activation. Our results show that intracerebroventricular (i.c.v.) administration of lipopolysaccharide (LPS) caused a heightened proinflammatory cytokine response (IL-1beta, IL-6, and TNFalpha) in the cerebellum 2h post i.c.v. injection in aged mice compared to adults. This amplified inflammatory profile was consistent with a brain region-dependent increase in reactive glial markers (MHC class II, TLR2 and TLR4). Moreover, LPS caused a prolonged sickness behavior response in aged mice that was paralleled by a protracted expression of brain cytokines in the cerebellum and hippocampus. Finally, central LPS injection caused amplified and prolonged IL-6 levels at the periphery of aged mice. Collectively, these data establish that activation of the central innate immune system leads to exacerbated neuroinflammation and prolonged sickness behavior in aged as compared to adult mice.
Key Biomarkers
Symptom Clusters
References (2)
- Exaggerated neuroinflammation and sickness behavior in aged mice after activation of the peripheral innate immune systemThe FASEB Journal · 2005
- Central and systemic endotoxin challenges exacerbate the local inflammatory response and increase neuronal death during chronic neurodegenerationJournal of Neuroscience · 2005
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