Abstract # 1859 A new LPS-based mouse model of chronic inflammation and depression

Abstract

Lipopolysaccharide (LPS) exposure is widely used to model depression in animals, but the transient nature of its effect and an occurrence of LPS tolerance limit its use for longitudinal studies. We tested a new schedule of injections designed to avoid tolerance and to induce neurobiological changes relevant for depression. Mice received intraperitoneal injections of escalating doses of LPS (from 0.33 to 0.83 mg/kg) once a week for 6 weeks. The results showed that LPS induced sickness behaviour every week. The peripheral blood cytokine response to LPS was modified by repeated injections. Some cytokines which were elevated by acute injection showed a lower magnitude of elevation (interleukin 6, tumor necrosis factor alpha), while others showed an increased response to repeated exposure. Interleukin 2 was only elevated by repeated LPS injections, while C-reactive protein was decreased. Anti-inflammatory cytokines were not elevated by chronic LPS exposure. This cytokine profile suggests a distinct mode of immune activation with minor signs of LPS tolerance. Assessment of adult hippocampal neurogenesis, relevant for depression neurobiology, found that exposure to escalating doses of LPS led to a reduction of neuroblasts maturation in the dentate gyrus. We conclude that minimal signs of tolerance and changes observed in hippocampal neurogenesis suggest that schedule of LPS injections used might be a suitable model to utilise in future studies looking into immunological aspects of mood disorders.