Low-dose lipopolysaccharide (LPS) inhibits aggressive and augments depressive behaviours in a chronic mild stress model in mice

Abstract

BackgroundAggression, hyperactivity, impulsivity, helplessness and anhedonia are all signs of depressive-like disorders in humans and are often reported to be present in animal models of depression induced by stress or by inflammatory challenges. However, chronic mild stress (CMS) and clinically silent inflammation, during the recovery period after an infection, for example, are often coincident, but comparison of the behavioural and molecular changes that underpin CMS vs a mild inflammatory challenge and impact of the combined challenge is largely unexplored. Here, we examined whether stress-induced behavioural and molecular responses are analogous to lipopolysaccharide (LPS)-induced behavioural and molecular effects and whether their combination is adaptive or maladaptive.MethodsChanges in measures of hedonic sensitivity, helplessness, aggression, impulsivity and CNS and systemic cytokine and 5-HT-system-related gene expression were investigated in C57BL/6J male mice exposed to chronic stress alone, low-dose LPS alone or a combination of LPS and stress.ResultsWhen combined with a low dose of LPS, chronic stress resulted in an enhanced depressive-like phenotype but significantly reduced manifestations of aggression and hyperactivity. At the molecular level, LPS was a strong inducer of TNFα, IL-1β and region-specific 5-HT2A mRNA expression in the brain. There was also increased serum corticosterone as well as increased TNFα expression in the liver. Stress did not induce comparable levels of cytokine expression to an LPS challenge, but the combination of stress with LPS reduced the stress-induced changes in 5-HT genes and the LPS-induced elevated IL-1β levels.ConclusionsIt is evident that when administered independently, both stress and LPS challenges induced distinct molecular and behavioural changes. However, at a time when LPS alone does not induce any overt behavioural changes per se, the combination with stress exacerbates depressive and inhibits aggressive behaviours.Electronic supplementary materialThe online version of this article (doi:10.1186/s12974-016-0572-0) contains supplementary material, which is available to authorized users.

Licofelone Attenuates LPS-induced Depressive-like Behavior in Mice: A Possible Role for Nitric Oxide

“…Based on the neuroinflammation hypothesis of depression, LPS-received mice are extensively used to evaluate the underlying mechanisms of depression (8,9). Licofelone ([2, 2-dimethyl-6-(4-chlorophenyl)-7-phenyl-2, 3, dihydro-1H-pyrrolizine-5-yl]-acetic acid) is a substrate analogue of AA and consequently inhibits 5-LOX, COX-1 and COX-2, reducing production of eicosanoid (10).…”

Immune System Challenge Improves Cognitive-Behavioural Responses and Reverses Malaria-Induced Cognitive Impairment in Mice

“…Antigens and/or vaccines were administered by different routes, in different regions of the animals’s body (Table 1). The doses administrated were defined based on dose-response protocols available in the literature capable of stimulating the murine immune system without imparting risk of death to mice immunized 5–12 .…”

“…Mice were challenged with 0.1 mg/kg of ecLPS O111: B4 (SIGMA-ALDERICH, L2630-10MG, Lot 025M4040V12140701) diluted in phosphate-buffered saline (PBS). Two ip inoculations were performed (Table 1) with a range of ten days between immunizations 12 (Fig. 2).…”

Dental status as a predictive factor in the development of squamous cell carcinoma of the oral mucosa

“…Исследования показывают [1][2][3], что многие заболевания полости рта значимо влияют на риски развития плоскоклеточного рака (ПЛР) слизистой оболочки полости рта (СОПР) [4][5][6]. Так, острые края зубов, протезов и пломб могут быть причиной хронической травмы СОПР [7,8], а наличие зубных отложений поддерживает хроническое воспаление пародонта [9,10], что в совокупности может инициировать развитие ПЛР.…”