Investigating the effects of chronic aerobic exercise on cognitive deficits and inflammatory markers in the sub-chronic phencyclidine mouse model for schizophrenia research

Cognitive impairments associated with schizophrenia (CIAS) are modelled in rodents using sub-chronic administration of phencyclidine (scPCP). Changes to inflammatory markers have been associated with CIAS in patients, while exercise can improve cognition clinically and pre-clinically. This study aimed to investigate the effect of exercise on cognition and inflammation in the scPCP mouse.Adult female c57 mice were dosed with vehicle (0.9% saline, n=28) or PCP (10mg/kg, n=28) once daily for 10 days and divided into sedentary or exercised groups. Exercised mice had running-wheel access for 1h daily, 5 days/week for 6 weeks, while sedentary mice remained in home-cages. To assess cognition, all mice underwent Novel Object Recognition (NOR) testing after 3 and 6 weeks. Plasma (baseline and 6 weeks) and brain (dorsal hippocampus at 6 weeks) samples were analysed for inflammatory markers.Vehicle-sedentary (3 and 6 weeks) and vehicle-exercised (6 weeks) mice demonstrated intact object recognition memory with a significant preference for the novel over the familiar object during NOR testing. scPCP-sedentary mice had deficits in both NOR tests, with no preference for the novel object. Exercise reversed the scPCP deficits in cognition at the 3-week timepoint. scPCP-treated mice had significantly increased levels of IL-12p70 and GM-CSF in the dorsal hippocampus, as well as increased GM-CSF and reduced IFNβ in plasma at baseline.Three weeks of daily aerobic exercise had a positive effect on cognition in scPCP mice. Changes to several inflammatory markers were observed after scPCP dosing, however, these were not resolved by exercise.