Lipopolysaccharide-induced depression-like model in mice: meta-analysis and systematic evaluation

Abstract

Depression is a complex and biologically heterogeneous disorder. Recent studies have shown that central nervous system (CNS) inflammation plays a key role in the development of depression. Lipopolysaccharide (LPS)-induced depression-like model in mice is commonly used to studying the mechanisms of inflammation-associated depression and the therapeutic effects of drugs. Numerous LPS-induced depression-like models in mice exist and differ widely in animal characteristics and methodological parameters. Here, we systematically reviewed studies on PubMed from January 2017 to July 2022 and performed cardinal of 170 studies and meta-analyses of 61 studies to support finding suitable animal models for future experimental studies on inflammation-associated depression. Mouse strains, LPS administration, and behavioral outcomes of these models have been assessed. In the meta-analysis, forced swimming test (FST) was used to evaluate the effect size of different mouse strains and LPS doses. The results revealed large effect sizes in ICR and Swiss mice, but less heterogeneity in C57BL/6 mice. For LPS intraperitoneal dose, the difference did not affect behavioral outcomes in C57BL/6 mice. However, in ICR mice, the most significant effect on behavioral outcomes was observed after the injection of 0.5 mg/kg LPS. Our results suggests that mice strains and LPS administration play a key role in the evaluation of behavioral outcomes in such models.

Mitochondrial dysfunction precedes hippocampal IL-1β transcription and cognitive impairments after low-dose lipopolysaccharide injection in aged mice

“…All studies were performed in C57BL/6 mice as they exhibit consistent behavioral responses, minimizing experimental variability [ 40 , 41 ]. Two age groups were used: young (8–10 weeks) and old (18–20 months), both sourced from Damul Science in Daejeon, South Korea.…”

The complex role of the chemokine CX3CL1/Fractalkine in major depressive disorder: A narrative review of preclinical and clinical studies

“…Another important limitation is the fact that a single dose of LPS is mimetic of an acute inflammatory response within the murine CNS ( Yin et al, 2023 ) that may not be an effective representation of the chronic low-grade inflammation observed in MDD patients ( Berk et al, 2013a , Berk et al, 2013b ). Acute inflammation may result in compensatory anti-inflammatory microglial mechanisms ( Qin et al, 2023 ) in which FKN may act as a mediator.…”

Mind, Mood and Microbiota—Gut–Brain Axis in Psychiatric Disorders

“…Bacterial lipopolysaccharides (LPSs), predominantly originating from Enterobacter spp., have been identified as playing a significant role in major depression. Notably, LPS levels are higher in patients with severe depression compared to healthy individuals [ 65 ]. These metabolites can enter the systemic circulation through permeability defects in the intestinal tight epithelial junctions, leading to leaky gut syndrome.…”