Changes in behaviour and cytokine expression upon a peripheral immune challenge
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1937503
- author
- Bay-Richter, Cecilie LU ; Janelidze, Shorena LU ; Hallberg, Ludvig LU and Brundin, Lena LU
- organization
- publishing date
- 2011
- 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
- pmid:21466824
- 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
- 2016-04-01 11:07:58
- date last changed
- 2022-04-20 17:17:10
@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}},
keywords = {{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}},
doi = {{10.1016/j.bbr.2011.03.060}},
volume = {{222}},
year = {{2011}},
}