The efficacy of systemic administration of lipopolysaccharide in modelling pre-motor Parkinson’s disease in C57BL/6 mice

•Systemic LPS induced olfactory impairment and anxiety-like behaviour in C57BL/6 mice.•Systemic LPS induced glial activation and oxidative stress in the olfactory bulb, hippocampus, midbrain and cerebellum.•Systemic LPS induced region-specific changes in the expression of NFκB, IL-1β, TH, α-synuclein and BDNF proteins.•This model is useful to elucidate early non-motor aspects of Parkinson’s disease. Parkinson’s disease (PD) is the second most common neurodegenerative disease, characterised by the loss of dopaminergic neurons in the substantia nigra. Mounting evidence indicates a crucial role of inflammation and concomitant oxidative stress in the disease progression. Therefore, the aim of this study was to investigate the ability of systemically administered lipopolysaccharide (LPS) to induce motor and non-motor symptoms of PD, inflammation, oxidative stress and major neuropathological hallmarks of the disease in regions postulated to be affected, including the olfactory bulb, hippocampus, midbrain and cerebellum. Twenty-one male C57BL/6 mice, approximately 20 weeks old, received a dose of 0.3 mg/kg/day of LPS systemically on 4 consecutive days and behavioural testing was conducted on days 14–18 post-treatment, followed by tissue collection. Systemically administered LPS increased latency time in the buried food seeking test (indicative of olfactory impairment), and decreased time spent in central zone of the open field (anxiety-like behaviour). However, there was no change in latency time in the rotarod test or the expression of tyrosine hydroxylase (TH) in the midbrain. Systemically administered LPS induced increased glial markers GFAP and Iba-1 and oxidative stress marker 3-nitrotyrosine (3-NT) in the olfactory bulb, hippocampus, midbrain and cerebellum, and there were region specific changes in the expression of NFκB, IL-1β, α-synuclein, TH and BDNF proteins. The model could be useful to further elucidate early non-motor aspects of PD and the possible mechanisms contributing to the non-motor deficits.