An exploratory study of gastrointestinal redox biomarkers in the presymptomatic and symptomatic Tg2576 mouse model of familial Alzheimer’s disease – phenotypic correlates and the effects of chronic oral D-galactose

Abstract

AbstractThe gut might play an important role in the etiopathogenesis of Alzheimer’s disease (AD) as gastrointestinal alterations often precede the development of neuropathological changes in the brain and correlate with disease progression in animal models. The gut has an immense capacity to generate free radicals whose role in the etiopathogenesis of AD is well known; however, it remains to be clarified whether gastrointestinal redox homeostasis is associated with the development of AD. The aim was to i) examine gastrointestinal redox homeostasis in the presymptomatic and symptomatic Tg2576 mouse model of AD; ii) investigate the effects of chronic oral D-galactose previously shown to alleviate cognitive deficits and metabolic changes in animal models of AD; iii) investigate the association between gastrointestinal redox biomarkers and behavioral alterations in Tg2576 mice. Presymptomatic Tg2576 have a heightened gastrointestinal electrophilic tone reflected in increased lipid peroxidation and activity of Mn/Fe-SOD. Chronic oral D-galactose treatment was associated with detrimental effects on redox homeostasis only in the wild-type controls. In the symptomatic stage, Tg2576 mice demonstrate compensated redox disbalance characterized by normalized lipid peroxidation and increased hydrogen peroxide dissociation capacity but diminished total antioxidant reserve alleviated with chronic oral D-galactose treatment. Conversely, D-galactose reduced antioxidant capacity and increased lipid peroxidation in the controls. Total antioxidant capacity was associated with greater spatial memory, while other biomarkers had a complex relationship with exploration, nesting, and grooming. Gut redox homeostasis might be involved in the development and progression of AD pathophysiology and should be further explored in this context.