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Brain Res. 2014 Mar 13;1552:55-63. doi: 10.1016/j.brainres.2014.01.012. Epub 2014 Jan 20.

Peripheral tumors alter neuroinflammatory responses to lipopolysaccharide in female rats.

Author information

1
Department of Psychology, Institute for Mind and Biology, University of Chicago, Chicago, IL 60637, USA. Electronic address: lpyter@uic.edu.
2
Department of Psychology, Institute for Mind and Biology, University of Chicago, Chicago, IL 60637, USA.
3
Department of Pathology, University of Chicago, Chicago, IL 60637, USA.

Abstract

Cancer is associated with an increased prevalence of depression. Peripheral tumors induce inflammatory cytokine production in the brain and depressive-like behaviors. Mounting evidence indicates that cytokines are part of a pathway by which peripheral inflammation causes depression. Neuroinflammatory responses to immune challenges can be exacerbated (primed) by prior immunological activation associated with aging, early-life infection, and drug exposure. This experiment tested the hypothesis that peripheral tumors likewise induce neuroinflammatory sensitization or priming. Female rats with chemically-induced mammary carcinomas were injected with either saline or lipopolysaccharide (LPS, 250μg/kg; i.p.), and expression of mRNAs involved in the pathway linking inflammation and depression (interleukin-1beta [Il-1β], CD11b, IκBα, indolamine 2,3-deoxygenase [Ido]) was quantified by qPCR in the hippocampus, hypothalamus, and frontal cortex, 4 or 24h post-treatment. In the absence of LPS, hippocampal Il-1β and CD11b mRNA expression were elevated in tumor-bearing rats, whereas Ido expression was reduced. Moreover, in saline-treated rats basal hypothalamic Il-1β and CD11b expression were positively correlated with tumor weight; heavier tumors, in turn, were characterized by more inflammatory, necrotic, and granulation tissue. Tumors exacerbated CNS proinflammatory gene expression in response to LPS: CD11b was greater in hippocampus and frontal cortex of tumor-bearing relative to tumor-free rats, IκBα was greater in hippocampus, and Ido was greater in hypothalamus. Greater neuroinflammatory responses in tumor-bearing rats were accompanied by attenuated body weight gain post-LPS. The data indicate that neuroinflammatory pathways are potentiated, or primed, in tumor-bearing rats, which may exacerbate future negative behavioral consequences.

KEYWORDS:

Cancer; Cytokine; Depression; Indolamine-2,3-deoxygenase; Microglia; Nf-κB

PMID:
24457042
PMCID:
PMC3967445
DOI:
10.1016/j.brainres.2014.01.012
[Indexed for MEDLINE]
Free PMC Article
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