Mammary tumors suppress aging-induced neuroinflammation in female Balb/c mice

Neuroinflammation confers changes in brain function (i.e., behavior) that are hypothesized to be adaptive in the short-term, but detrimental (e.g., depression, anxiety) if they persist. Both peripheral tumor growth (outside of the brain) and natural aging independently cause neuroinflammation in rodents, which is corroborated by clinical studies. Mammary tumor effects on neuroinflammation and behavior, however, are typically studied in young rodents, whereas most breast cancer patients are middle-aged. Therefore, the existing literature likely underestimates the resulting neuroinflammation that may occur in clinical cancer populations. The present study tested the hypothesis that aging exacerbates mammary tumor-induced neuroinflammation in female mice. Aging (16 months and ovariectomized) increased body and spleen masses, whereas tumors grew faster and increased spleen mass in young mice (12 weeks) only. Tumors (IL-6, IL-10, TNFα, MCP-1, CXCL1, IP-10) and aging (IL-10, IFNγ) independently increased circulating inflammatory markers, although these variables were only significantly additive in one case (TNFα). In contrast to our prediction, the interaction between tumors and aging resulted in reduced mRNA and protein expression of select inflammatory markers in the hippocampus of tumor-bearing aged mice relative to aged controls. These results indicate that tumors reduce inflammatory activation in the brains of aged mice, a deficit that is likely disadvantageous. Further understanding of how aging and cancer interact to affect brain function is necessary to provide clinically-relevant results and identify mechanisms underlying persistent behavioral issues hampering adult cancer patients.