Exploration of the cognitive functions of females in a mouse model of chronic neuroinflammation

Abstract

AbstractBackgroundChronic neuroinflammation has been identified as a common feature of many neurodegenerative diseases, such as Alzheimer’s disease (Kempuraj et al., 2016). Sex has been shown to strongly influence the development as well as the clinical expression of neurodegenerative and neuroinflammatory diseases . The GFAP‐IL6 mouse is a useful model to study chronic neuroinflammation and its consequences. These mice exhibit increased levels of neuroinflammatory markers, neurodegeneration, as well as motor deficits (Campbell et al., 1993; Chiang et al., 1994; Gyengesi et al., 2019). Although previous studies have identified some cognitive impairments in these animals (Heyser et al., 1997), more work is needed to fully characterised this model at a behavioural level.MethodCognitive tests exploring anxiety such as the elevated plus‐maze (EPM), light/dark box, and spatial learning and memory such as the Barnes maze and Y‐maze, were performed on female GFAP‐IL6 mice and their litter mate control wild‐type (WT) from 12 months of age. Tests were recorded using AnyMaze® and results analysed in IBM SPSS® software with one or two‐way ANOVAs. This study was completed with immunochemistry and RT‐qPCR in brain regions implicated in anxiety, learning and memory.ResultWe found that the GFAP‐IL6 mice travelled a significantly higher percentage of distance in the opened arm of the EPM than the WT (WT=9.48%, GFAP‐IL6=18.03%, p<0.01), and a lower percentage in the closed arm than the WT (WT=63.13%, GFAP‐IL6=53.70%, p<0.05). No genotype effect was found in the preference for the light compartment during the light/dark box test. In the Y‐maze, the GFAP‐IL6 mice spent a significantly lower percentage of time in the novel arm compared to the WT (WT=45.06%, GFAP‐IL6=27.97%, p<0.01). During the acquisition phase of the Barnes maze, all mice were able to learn the location of the escape hole. However, there was a significant effect of genotype (p<0.01), with the GFAP‐IL6 mice exhibiting higher latencies to enter the escape hole than the WT. No significant difference was found during the probe testConclusionThese results suggest that female GFAP‐IL6 mice exhibit a less anxious phenotype but seem to present impaired spatial memory compared to female WT.