Exploratory Study of Gastrointestinal Redox Biomarkers in the Presymptomatic and Symptomatic Tg2576 Mouse Model of Familial Alzheimer's Disease: Phenotypic Correlates and Effects of Chronic Oral d-Galactose

Scientific paper - Original scientific paper

• Author: Jan Homolak
• Author: Ana Babić Perhoč
• Author: Ana Knezović
• Author: Jelena Osmanović Barilar
• Author: Davor Virag
• Author: Melita Šalković-Petrišić
• Author's institution: University of Zagreb; School of Medicine; (Department of Pharmacology)
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Basic Medical Sciences; Pharmacology

Abstract (english)

The 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 oral d-galactose previously shown to alleviate cognitive deficits and metabolic changes in animal models of AD and reduce gastrointestinal oxidative stress; and (iii) investigate the association between gastrointestinal redox biomarkers and behavioral alterations in Tg2576 mice. In the presymptomatic stage, Tg2576 mice displayed an increased gastrointestinal electrophilic tone, characterized by higher lipid peroxidation and elevated Mn/Fe-SOD activity. In the symptomatic stage, these alterations are rectified, but the total antioxidant capacity is decreased. Chronic oral d-galactose increased the antioxidant capacity and reduced lipid peroxidation in the Tg2576 but had the opposite effects in the wild-type animals. The total antioxidant capacity of the gastrointestinal tract was associated with greater spatial memory. Gut redox homeostasis might be involved in the development and progression of AD pathophysiology and should be further explored in this context.

• Keywords (english): Alzheimer Disease / metabolism; Amyloid beta-Peptides / metabolism; Animals; Antioxidants / metabolism; Disease Models, Animal; Galactose / pharmacology; Mice; Mice, Transgenic; Oxidation-Reduction
• Language: english
• Publication type: Scientific paper - Original scientific paper
• Publication status: Published
• Peer review: Peer review
• Publication version: Published version
• Journal title: ACS Chemical Neuroscience
• Numbering: vol. 14, no. 22, pp. 4013-4025
• p-ISSN: 1948-7193
• e-ISSN: 1948-7193
• DOI: https://doi.org/10.1021/acschemneuro.3c00495
• URN:NBN: urn:nbn:hr:105:023423
• Publication: 2023-11-15
• Document URL: https://pubs.acs.org/doi/10.1021/acschemneuro.3c00495
• Type of resource: Text
• Access conditions: Open access
• Created on: 2024-05-06 08:26:05