A study of the effects of chronic neuroinflammation on cognition and behaviour in the GFAP-IL6 transgenic mouse and investigation of the flavonoid apigenin as a neuroprotective agent

Abstract

Neuroinflammation is a prominent feature of most neurodegenerative and affective disorders and has been increasingly implicated as a contributing factor in the disease development. The inflammatory process is closely linked with multiple neurodegenerative pathways and represents an important therapeutic target in halting or reversing disease progression. This study explored the cognitive and behavioural effects of chronic neuroinflammation in the glial fibrillary acidic protein promoter-interleukin 6 (GFAP-IL6) transgenic mouse in which the pro-inflammatory cytokine interleukin 6 (IL-6) is overexpressed causing low level, chronic inflammation localised to the brain. Additionally the anti-inflammatory, anti-oxidant and neuroprotective potential of the dietary bioflavanoid apigenin was investigated to determine whether any deficits in behaviour and cognition could be rescued. Male and female heterozygous GFAP-IL6 mice (n=32) and their non-transgenic littermates (C57/BL6J) (n=36) were introduced to either an apigenin enriched pellet diet (40mg/kg daily dose) or control pellet diet at the age of 3 months. After 3 months of feeding (6 months of age) the mice were subjected to a behavioural test battery including the elevated plus maze (EPM), open field test (OF), Barnes maze (BM) and functional observational tests. The results showed that at 6 months of age, GFAP-IL6 mice exhibited alterations in anxiety-related behaviour in the EPM and OF, presenting a tendency toward an anxiolytic-like phenotype and demonstrated impairments in memory and spatial learning in the BM. GFAP-IL6 mice also displayed an ataxic phenotype and exhibited reduced locomotor activity compared to wild-type (WT) controls. The effect of apigenin on anxiety-related behaviours were mixed, being sedative-like in reducing locomotion and explorative behaviour in the EPM and OF, and anxiolytic-like in reducing risk assessment behaviour. Cognition improving properties are indicated for apigenin in the BM probe trial, enhancing recall of the target hole location, particularly among GFAP-IL6 mice. Interestingly, apigenin was additionally associated with increased food consumption and weight gain, suggesting potential as an appetite stimulant.

Date of Award	2018
Original language	English