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Changes in behaviour and cytokine expression upon a peripheral immune challenge

Bay-Richter, Cecilie LU ; Janelidze, Shorena LU ; Hallberg, Ludvig LU and Brundin, Lena LU (2011) In Behavioural Brain Research 222(1). p.193-199
Abstract
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... (More)
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-1β, IL-6 and TNF-α 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-1β mRNA had increased even further, as well as IL-1β CSF levels. IL-6 and TNF-α 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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Depression, Sickness, Cytokines, Lipopolysaccharide
in
Behavioural Brain Research
volume
222
issue
1
pages
193 - 199
publisher
Elsevier
external identifiers
  • wos:000291418400024
  • pmid:21466824
  • scopus:79954603875
ISSN
0166-4328
DOI
10.1016/j.bbr.2011.03.060
language
English
LU publication?
yes
id
275058f8-1190-4a6d-9e3a-b76961fa7330 (old id 1937503)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/21466824?dopt=Abstract
date added to LUP
2012-01-18 16:00:09
date last changed
2017-07-30 03:27:45
@article{275058f8-1190-4a6d-9e3a-b76961fa7330,
  abstract     = {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-1β, IL-6 and TNF-α 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-1β mRNA had increased even further, as well as IL-1β CSF levels. IL-6 and TNF-α 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.},
  author       = {Bay-Richter, Cecilie and Janelidze, Shorena and Hallberg, Ludvig and Brundin, Lena},
  issn         = {0166-4328},
  keyword      = {Depression,Sickness,Cytokines,Lipopolysaccharide},
  language     = {eng},
  number       = {1},
  pages        = {193--199},
  publisher    = {Elsevier},
  series       = {Behavioural Brain Research},
  title        = {Changes in behaviour and cytokine expression upon a peripheral immune challenge},
  url          = {http://dx.doi.org/10.1016/j.bbr.2011.03.060},
  volume       = {222},
  year         = {2011},
}