Prolonged neuroinflammation after lipopolysaccharide exposure in aged rats.

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 st...

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Main Authors: Hui Qun Fu, Ting Yang, Wei Xiao, Long Fan, Yan Wu, Niccolò Terrando, Tian Long Wang
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2014-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC4149545?pdf=render
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author Hui Qun Fu
Ting Yang
Wei Xiao
Long Fan
Yan Wu
Niccolò Terrando
Tian Long Wang
author_facet Hui Qun Fu
Ting Yang
Wei Xiao
Long Fan
Yan Wu
Niccolò Terrando
Tian Long Wang
author_sort Hui Qun Fu
collection DOAJ
description 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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spelling doaj.art-73417f6283bb4918b64fd7d9e52836f72022-12-22T03:40:16ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0198e10633110.1371/journal.pone.0106331Prolonged neuroinflammation after lipopolysaccharide exposure in aged rats.Hui Qun FuTing YangWei XiaoLong FanYan WuNiccolò TerrandoTian Long WangInflammation 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.http://europepmc.org/articles/PMC4149545?pdf=render
spellingShingle Hui Qun Fu
Ting Yang
Wei Xiao
Long Fan
Yan Wu
Niccolò Terrando
Tian Long Wang
Prolonged neuroinflammation after lipopolysaccharide exposure in aged rats.
PLoS ONE
title Prolonged neuroinflammation after lipopolysaccharide exposure in aged rats.
title_full Prolonged neuroinflammation after lipopolysaccharide exposure in aged rats.
title_fullStr Prolonged neuroinflammation after lipopolysaccharide exposure in aged rats.
title_full_unstemmed Prolonged neuroinflammation after lipopolysaccharide exposure in aged rats.
title_short Prolonged neuroinflammation after lipopolysaccharide exposure in aged rats.
title_sort prolonged neuroinflammation after lipopolysaccharide exposure in aged rats
url http://europepmc.org/articles/PMC4149545?pdf=render
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AT longfan prolongedneuroinflammationafterlipopolysaccharideexposureinagedrats
AT yanwu prolongedneuroinflammationafterlipopolysaccharideexposureinagedrats
AT niccoloterrando prolongedneuroinflammationafterlipopolysaccharideexposureinagedrats
AT tianlongwang prolongedneuroinflammationafterlipopolysaccharideexposureinagedrats