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

• Published in: Psychopharmacology Vol. 236; no. 10; pp. 2975 - 2982
• Main Authors: Vichaya, Elisabeth G., Gross, Phillip S., Estrada, Darlene J., Cole, Steve W., Grossberg, Aaron J., Evans, Scott E., Tuvim, Michael J., Dickey, Burton F., Dantzer, Robert
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.10.2019; Springer; Springer Nature B.V
• Subjects: Analysis; Animals; Bacterial infections; Biomedical and Life Sciences; Biomedicine; Body weight; Body weight loss; Brain - drug effects; Brain - immunology; Brain - metabolism; Cytokines - metabolism; Depression - chemically induced; Depression - immunology; Depression - metabolism; Depression, Mental; Food consumption; Genotypes; Health aspects; Illness Behavior - drug effects; Illness Behavior - physiology; Immune response; Infection; Inflammation; Inflammation - chemically induced; Inflammation - immunology; Inflammation - metabolism; Lipocalin; Lipocalin-2 - deficiency; Lipopolysaccharides; Lipopolysaccharides - toxicity; Male; Medical research; Medicine, Experimental; Mental depression; Mice; Mice, Inbred C57BL; Mice, Knockout; Mitogens; Molecular modelling; Motor Activity - drug effects; Motor Activity - physiology; Neurosciences; Original Investigation; Pharmacology/Toxicology; Psychiatry; Ribonucleic acid; RNA; RNA sequencing; Rodents; Sucrose; Wheel running; Lipopolysaccharide; Innate immunity; Depression; Inflammation; Sickness behavior; Lipocalin-2
• ISSN: 0033-3158; 1432-2072; 1432-2072
• DOI: 10.1007/s00213-019-05190-7

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.