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Updated: Jul 14, 2026
Injections of Lipopolysaccharide into Mice to Mimic Entrance of Microbial-derived Products After Intestinal Barrier Breach
Published on: May 2, 2018
c-Fos immunoreactivity induced by intraperitoneal LPS administration is reduced in the brain of mice lacking the
M Dallaporta1, E Pecchi, C Jacques
1Laboratoire de Physiologie Neurovégétative, UMR 6153 CNRS-1147 INRA, Université Paul Cézanne, Marseille, France.
Abstract:
The aim of the present study was to investigate the impact of the deletion of the microsomal prostaglandin E synthase-1 (mPGES-1) gene on lipopolysaccharide (LPS)-induced neuronal activation in central nervous structures. The mPGES-1 catalyses the conversion of COX-derived PGH(2) to PGE(2) and has been described as a regulated enzyme whose expression is stimulated by proinflammatory agents. Using the immediate-early gene c-fos as a marker of neuronal activation, we determined whether deletion of the mPGES-1 gene altered the neuronal activation induced by LPS in structures classically recognized as immunosensitive regions. No significant difference in the c-Fos immunostaining was observed in the brain of saline-treated mPGES-1+/+, mPGES-1+/- and mPGES-1-/- mice. However, we observed that LPS-induced neuronal activation was reduced in most of the centres known as immunosensitive nuclei in mPGES-1-/- mice compared with heterozygous and wild-type mice. The decrease in the number of c-Fos positive nuclei occurred particularly in the caudal ventrolateral medulla, the medial, intermediate and central parts of the nucleus tractus solitarius, area postrema, parabrachial nucleus, locus coeruleus, paraventricular nucleus of the hypothalamus, ventromedial preoptic area, central amygdala, bed nucleus of the stria terminalis and to a lesser extent in the ventrolateral part of the nucleus tractus solitarius and rostral ventrolateral medulla. These results suggest that the mPGES-1 enzyme is strongly needed to provide sufficient PGE(2) production required to stimulate immunosensitive brain regions and they are discussed with regard to the recent works reporting impaired sickness behavior in mPGES-1-/- mice.
Insights
Mice lacking the microsomal prostaglandin E synthase-1 (mPGES-1) gene show reduced neuronal activation in response to lipopolysaccharide (LPS). This suggests mPGES-1 is crucial for stimulating brain regions involved in immune responses.
Area of Science:
- Neuroscience
- Immunology
- Biochemistry
Background:
- Microsomal prostaglandin E synthase-1 (mPGES-1) synthesizes prostaglandin E2 (PGE2), a key mediator of inflammation.
- mPGES-1 expression is upregulated by pro-inflammatory stimuli like lipopolysaccharide (LPS).
- Neuronal activation in central nervous structures is a hallmark of immune responses.
Purpose of the Study:
- To investigate the role of mPGES-1 in LPS-induced neuronal activation within the central nervous system.
- To determine if the absence of mPGES-1 affects the expression of neuronal activation markers in response to LPS.
Main Methods:
- Utilized mPGES-1 knockout (mPGES-1-/-), heterozygous (mPGES-1+/-), and wild-type (mPGES-1+/+) mice.
- Administered lipopolysaccharide (LPS) or saline to mice.
- Assessed neuronal activation by quantifying c-Fos positive nuclei in specific brain regions using immunostaining.
Main Results:
- No significant difference in c-Fos expression was observed between genotypes in saline-treated mice.
- LPS administration induced significantly reduced c-Fos expression in most immunosensitive brain nuclei of mPGES-1-/- mice compared to controls.
- Key brain regions showing reduced activation include the ventrolateral medulla, nucleus tractus solitarius, area postrema, and amygdala.
Conclusions:
- The mPGES-1 enzyme is essential for adequate prostaglandin E2 (PGE2) production necessary to stimulate immunosensitive brain regions during inflammatory responses.
- These findings align with previous reports of impaired sickness behavior in mPGES-1 deficient mice.
