期刊
BEHAVIOURAL BRAIN RESEARCH
卷 222, 期 1, 页码 193-199出版社
ELSEVIER
DOI: 10.1016/j.bbr.2011.03.060
关键词
Depression; Sickness; Cytokines; Lipopolysaccharide
资金
- Swedish Research Council [K2009-61X-21524-01-1]
- Swedish Brain Foundation
- Soderstrom-Konig Foundation
- Sjobring Foundation
- Fysiografiska Society
- province of Scania state grants (ALF)
Depression is frequently associated with inflammation. Animal studies have shown that peripheral inflammation induces depressive-like behaviour, but the underlying mechanisms remain unclear. A distinction between sickness- and depressive-like behaviour has been proposed. We hypothesize that the behavioural distinction is due to changes in the central production of immune mediators. As a model of peripheral inflammation, we administered lipopolysaccharide (LPS) intraperitoneally daily for 4 days in rats. The effect of LPS on sickness- and depressive-like behaviour was assessed. We examined protein levels and mRNA expression of cytokines and cyclooxygenase (COX) enzymes in serum, cerebrospinal fluid (CSF) and specific brain regions. Two hours post-LPS, the rats displayed sickness behaviour and cytokine levels were elevated in both serum and CSF. This was paralleled by specific alterations of mRNA transcription of IL-1 beta, IL-6 and TNF-alpha in frontal cortex, hippocampus and striatum. Twenty-four hours post-LPS the rats showed depressive-like behaviour and peripheral cytokine levels were back close to baseline. In contrast, the central transcription of IL-1 beta mRNA had increased even further, as well as IL-1 beta CSF levels. IL-6 and TNF-alpha transcription was unaltered compared to controls. COX enzymes were downregulated in the hippocampus during sickness behaviour and unaltered during depressive-like behaviour. Our results show for the first time that a peripheral immune challenge induces a region specific transcription of cytokines and COX-enzymes in the brain, at time-points corresponding to behavioural sickness and depression. When the peripheral inflammation and sickness behaviour had ceased, a production of proinflammatory cytokines remained within the brain parenchyma. (C) 2011 Elsevier B.V. All rights reserved.
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