Lipocalin-2 is dispensable in inflammation-induced sickness and depression-like behavior

Elisabeth G. Vichaya, Phillip S. Gross, Darlene J. Estrada, Steve W. Cole, Aaron J. Grossberg, Scott E. Evans, Michael J. Tuvim, Burton F. Dickey, Robert Dantzer

Research output: Contribution to journalArticlepeer-review

17 Scopus citations


Rationale: While the relationship between inflammation and depression is well-established, the molecular mechanisms mediating this relationship remain unclear. RNA sequencing analysis comparing brains of vehicle- and lipopolysaccharide-treated mice revealed LCN2 among the most dysregulated genes. As LCN2 is known to be an important regulator of the immune response to bacterial infection, we investigated its role in the behavioral response to lipopolysaccharide. Objective: To explore the role of LCN2 in modulating behavior following lipopolysaccharide administration using wild type (WT) and lcn2−/− mice. Methods: Using a within-subjects design, mice were treated with 0.33 mg/kg liposaccharide (LPS) and vehicle. Primary outcome measures included body weight, food consumption, voluntary wheel running, sucrose preference, and the tail suspension test. To evaluate the inflammatory response, 1 week later, mice were re-administered either vehicle or LPS and terminated at 6 h. Results: While lcn2−/− mice had increased baseline food consumption and body weight, they showed a pattern of reduced food consumption and weight loss similar to WT mice in response to LPS. WT and lcn2−/− mice both recovered voluntary activity on the fourth day following LPS. LPS induced equivalent reductions in sucrose preference and TST immobility in the WT and lcn2−/− mice. Finally, there were no significant effects of genotype on inflammatory markers. Conclusions: Our data demonstrate that lcn2 is dispensable for sterile inflammation-induced sickness and depression-like behavior. Specifically, lcn2−/− mice displayed sickness and immobility in the tail suspension test comparable to that of WT mice both in terms of intensity and duration.

Original languageEnglish (US)
Pages (from-to)2975-2982
Number of pages8
Issue number10
StatePublished - Oct 1 2019


  • Depression
  • Inflammation
  • Innate immunity
  • Lipocalin-2
  • Lipopolysaccharide
  • Sickness behavior

ASJC Scopus subject areas

  • Pharmacology


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