Study of the inflammatory variation induced by bacterial lipopolysaccharide on Nothobranchius furzeri

Details

Supervisors

Page, Melissa ; Larondelle, Yvan

Faculty

Faculté des bioingénieurs

Degree label

Master [120] : bioingénieur en sciences agronomiques, à finalité spécialisée

Abstract

Thanks to advancements in healthcare, the average global lifespan has significantly increased. However, this means that we continue to be faced with the challenges associated with individuals reaching ages that are associated with increased risk of various diseases such as metabolic syndrome, cancers, neurodegenerative disorders, and cardiovascular diseases. Aging is currently believed to be due to twelve hallmarks, among which chronic inflammation is one of the latest additions. While inflammation serves as a natural defense mechanism, unresolved inflammation can lead to chronic inflammation with detrimental effects on immune cells. A new term, inflammaging, has been introduced to describe age-related chronic inflammation, characterizing by an increase in pro-inflammatory cytokine production and a decrease in anti-inflammatory cytokine production. The aim of this thesis was to assess the gene response to LPS-induced inflammation at two different ages in the liver and brain of Nothobranchius furzeri. This work was carried out as part of a larger research theme, addressing whether N. furzeri are good models to explore inflammation. Previous research from our group has suggested that aging alone is not enough to alter the expression of genes associated with inflammatory signaling. This is the first study examining age-related gene expression response to LPS injection using N.furzeri. Intraperitoneal injections of bacterial lipopolysaccharide (E. coli O55:B5) were administrated to two different age group (6 and 20 weeks) at three distinct concentrations (10, 20, and 30µg/g of fish body weight). Subsequently, the liver and brain expression of four inflammatory genes (IL-10, APOA-1, IL-8, TLR2) was evaluated using real-time qPCR. The results showed an increase in the expression of the anti-inflammatory gene IL-10 in response to different LPS concentrations in the brains of young fish, while this expression remains stable in older fish. However, the LPS concentration did not influence the expression of the APOA-1, IL-8 and TLR2 genes. Nevertheless, an age effect was observed for IL-8, both in the brain and the liver, as well as for TLR2, but only in the brain. Significant interactions between LPS concentrations and age were noted for the IL-10 gene in brain tissue and for IL-8 gene in liver tissue. These findings underscore the complexity of the inflammatory response in aging, highlighting distinct age-related differences in gene expression in response to LPS.