Repeated lipopolysaccharide exposure modifies immune and sickness behaviour response in an animal model of chronic inflammation

TY - JOUR

T1 - Repeated lipopolysaccharide exposure modifies immune and sickness behaviour response in an animal model of chronic inflammation

AU - Musaelyan, Ksenia

AU - Aldridge, S. E.

AU - Du Preez, Andrea

AU - Egeland, Martin Tor Lutzhoft

AU - Zunszain, Patricia Ana

AU - Pariante, Carmine Maria

AU - Thuret, Sandrine

AU - Fernandes, Catherine

PY - 2017/11/8

Y1 - 2017/11/8

N2 - Repeated lipopolysaccharide (LPS) exposure is often used in longitudinal preclinical models of depression. However, the potential phenotypic differences from acute depression-mimicking effects are rarely described. This study compared chronic LPS administration of doses previously used in depression research to a new mode of escalating dose injections. Adult male BALB/c mice (n=8/group) were injected intraperitoneally with either a single 0.83 mg/kg dose, a repeated 0.1 mg/kg LPS dose or a dose which escalated weekly from 0.33 to 0.83 mg/kg LPS for six weeks. The escalating LPS group demonstrated most features of sickness behaviour such as weight loss and reduction in food intake every week, whist this effect was not sustained in other groups. Moreover, only in the escalating LPS group did most peripheral plasma cytokines levels, measured using Luminex® multiplex technology, such as interleukin 6 (IL-6), tumor necrosis factor α and IL-2 remain over 3 fold elevated on the 6th week. In addition, exposure to escalating doses led to a reduction of neuroblast maturation in the dentate gyrus relevant for depression neurobiology. Therefore, this mode of injections might be useful in the studies attempting to replicate neurobiological aspects of the chronic inflammatory state observed in mood disorders.

AB - Repeated lipopolysaccharide (LPS) exposure is often used in longitudinal preclinical models of depression. However, the potential phenotypic differences from acute depression-mimicking effects are rarely described. This study compared chronic LPS administration of doses previously used in depression research to a new mode of escalating dose injections. Adult male BALB/c mice (n=8/group) were injected intraperitoneally with either a single 0.83 mg/kg dose, a repeated 0.1 mg/kg LPS dose or a dose which escalated weekly from 0.33 to 0.83 mg/kg LPS for six weeks. The escalating LPS group demonstrated most features of sickness behaviour such as weight loss and reduction in food intake every week, whist this effect was not sustained in other groups. Moreover, only in the escalating LPS group did most peripheral plasma cytokines levels, measured using Luminex® multiplex technology, such as interleukin 6 (IL-6), tumor necrosis factor α and IL-2 remain over 3 fold elevated on the 6th week. In addition, exposure to escalating doses led to a reduction of neuroblast maturation in the dentate gyrus relevant for depression neurobiology. Therefore, this mode of injections might be useful in the studies attempting to replicate neurobiological aspects of the chronic inflammatory state observed in mood disorders.

KW - Lipopolysaccharide, chronic inflammation, sickness behaviour, adult neurogenesis, hippocampus, cytokine, microglia

U2 - 10.1177/0269881117746902

DO - 10.1177/0269881117746902

M3 - Article

SN - 0269-8811

VL - 32

SP - 236

EP - 247

JO - Journal of Psychopharmacology

JF - Journal of Psychopharmacology

IS - 2

ER -