, Volume 236, Issue 10, pp 2975–2982 | Cite as

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

  • Elisabeth G. VichayaEmail author
  • Phillip S. Gross
  • Darlene J. Estrada
  • Steve W. Cole
  • Aaron J. Grossberg
  • Scott E. Evans
  • Michael J. Tuvim
  • Burton F. Dickey
  • Robert Dantzer
Original Investigation



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.


To explore the role of LCN2 in modulating behavior following lipopolysaccharide administration using wild type (WT) and lcn2−/− mice.


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.


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.


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.


Lipocalin-2 Inflammation Lipopolysaccharide Innate immunity Depression Sickness behavior 


Funding information

This research was supported by the National Institutes of Health (R01 CA193522 and R21 MH104694 to R.D., R01 NS073939 to A.K., R.D., and C.J.H., and an MD Anderson Cancer Center Support Grant (P30 CA016672)).

Compliance with ethical standards

All protocols were approved by the University of Texas MD Anderson Cancer Center Institutional Animal Care and Use Committee.

Conflict of interest

Robert Dantzer has received honoraria from Danone Nutricia Research and Pfizer that are unrelated to the present study. All remaining authors declare no competing interests.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Elisabeth G. Vichaya
    • 1
    Email author
  • Phillip S. Gross
    • 1
  • Darlene J. Estrada
    • 1
  • Steve W. Cole
    • 2
  • Aaron J. Grossberg
    • 3
  • Scott E. Evans
    • 4
  • Michael J. Tuvim
    • 4
  • Burton F. Dickey
    • 4
  • Robert Dantzer
    • 1
  1. 1.Department of Symptom Research, Division of Internal MedicineUniversity of Texas MD Anderson Cancer CenterHoustonUSA
  2. 2.Departments of Medicine and Psychiatry & Biobehavioral Sciences, Jonsson Comprehensive Cancer Center and Norman Cousins CenterUCLA School of MedicineLos AngelesUSA
  3. 3.Department of Radiation Medicine, School of MedicineOregon Health & Sciences UniversityPortlandUSA
  4. 4.Department of Pulmonary Medicine, Division of Internal MedicineUniversity of Texas MD Anderson Cancer CenterHoustonUSA

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