Peripheral tumors alter neuroinflammatory responses to lipopolysaccharide in female rats.
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.
Department of Psychology, Institute for Mind and Biology, University of Chicago, Chicago, IL 60637, USA. Electronic address: lpyter@uic.edu.
Leah M
LM
Pyter
Department of Psychology, Institute for Mind and Biology, University of Chicago, Chicago, IL 60637, USA.
Sarah
S
El Mouatassim Bih
Department of Pathology, University of Chicago, Chicago, IL 60637, USA.
Husain
H
Sattar
Department of Psychology, Institute for Mind and Biology, University of Chicago, Chicago, IL 60637, USA.
Brian J
BJ
Prendergast
D000818:Animals; D039481:CD11b Antigen / Q000096:biosynthesis / Q000235:genetics; D003863:Depression / Q000209:etiology / Q000235:genetics / Q000276:immunology*; D015536:Down-Regulation / Q000187:drug effects; D019446:Endotoxemia / Q000235:genetics / Q000276:immunology* / Q000523:psychology; D004731:Endotoxins / Q000633:toxicity*; D004790:Enzyme Induction / Q000187:drug effects; D005260:Female; D005625:Frontal Lobe / Q000187:drug effects / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism*; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000096:biosynthesis / Q000235:genetics; D007249:Inflammation / Q000139:chemically induced / Q000235:genetics / Q000276:immunology* / Q000523:psychology; D053583:Interleukin-1beta / Q000096:biosynthesis / Q000235:genetics; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced / Q000276:immunology* / Q000523:psychology; D012333:RNA, Messenger / Q000096:biosynthesis; D012334:RNA, Neoplasm; D051381:Rats; D017208:Rats, Wistar; D047368:Tumor Burden / Q000187:drug effects; D015430:Weight Gain
D039481:CD11b Antigen; D004731:Endotoxins; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D053583:Interleukin-1beta; D012333:RNA, Messenger; D012334:RNA, Neoplasm; C044101:endotoxin, Escherichia coli
Cancer; Cytokine; Depression; Indolamine-2,3-deoxygenase; Microglia; Nf-κB