Abstract |
Inflammation is a hallmark of several disease states ranging from neurodegeneration to sepsis but is also implicated in physiological processes like ageing. Non-resolving inflammation and prolonged neuroinflammation are unclear processes implicated in several conditions, including ageing. In this study we studied the long-term effects of endotoxemia, as systemic lipopolysaccharide (LPS) injection, focusing on the role of astrocyte activation and cytokine release in the brain of aged rats. A single dose of LPS (2 mg/kg) or 0.9% saline was injected intraperitoneally in aged rats. Levels of pro-inflammatory cytokines (TNFα and IL-1β) and NF-κB p65 activation were measured systemically and in hippocampal tissue. Astrocytes and cytokines release in the CNS were detected via double immunofluorescence staining at different time-points up to day 30. Serum levels of TNFα and IL-1β were significantly increased acutely after 30 minutes (p<0.001) and up to 6 hours (p<0.001) following LPS-injection. Centrally, LPS-treated rats showed up-regulated mRNA expression and protein levels of pro-inflammatory cytokines in the hippocampus. These changes associated with astrogliosis in the hippocampus dentate gyrus (DG), IL-1β immunoreactivity and elevated NF-κB p65 expression up to day 30 post LPS exposure. Overall, these data demonstrate that LPS induces prolonged neuroinflammation and astrocyte activation in the hippocampus of aged rats. Hippocampal NF-κB p65 and excessive astrocytes-derived IL-1β release may play a pivotal role in regulating long-lasting neuroinflammation.
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Authors | Hui Qun Fu, Ting Yang, Wei Xiao, Long Fan, Yan Wu, Niccolò Terrando, Tian Long Wang |
Journal | PloS one
(PLoS One)
Vol. 9
Issue 8
Pg. e106331
( 2014)
ISSN: 1932-6203 [Electronic] United States |
PMID | 25170959
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- IL1B protein, mouse
- Interleukin-1beta
- Lipopolysaccharides
- Rela protein, mouse
- Transcription Factor RelA
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Topics |
- Aging
(genetics, metabolism)
- Animals
- Astrocytes
(pathology)
- Gene Expression Regulation
(drug effects)
- Hippocampus
(metabolism, pathology)
- Inflammation
(chemically induced, metabolism, pathology)
- Interleukin-1beta
(genetics, metabolism)
- Lipopolysaccharides
(administration & dosage)
- Male
- Rats
- Rats, Wistar
- Signal Transduction
(drug effects)
- Transcription Factor RelA
(genetics, metabolism)
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