Increased oxidative stress contributes to enhance brain amyloidogenesis and blunts energy metabolism in sucrose-fed rat: effect of AMPK activation

• Published in: Scientific reports 2021-10, Vol.11 (1), p.19547-19547, Article 19547
• Main Authors: Camacho-Castillo, Luz, Phillips-Farfán, Bryan V., Rosas-Mendoza, Gabriela, Baires-López, Aidee, Toral-Ríos, Danira, Campos-Peña, Victoria, Carvajal, Karla
• Format: Article
• Language: English
• Subjects: 631/378; 631/443/319; 631/45; 631/45/275; 692/308/1426; AKT protein; Alzheimer Disease - etiology; Alzheimer Disease - metabolism; Alzheimer Disease - pathology; Alzheimer's disease; AMP-Activated Protein Kinases - metabolism; Amyloid beta-Peptides - metabolism; Amyloid precursor protein; Amyloidogenesis; Animal Feed; Animal tissues; Animals; Antioxidants; Antioxidants - metabolism; Biomarkers; Catalase; Creatine; Creatine kinase; Disease Models, Animal; Disease Susceptibility; Energy metabolism; Energy Metabolism - drug effects; Gene expression; Gene Expression Regulation, Enzymologic; Hippocampus; Humanities and Social Sciences; Hypothalamus; Kinases; Lipid peroxidation; Metabolic disorders; Metabolic rate; Metabolic syndrome; Metabolic Syndrome - etiology; Metabolic Syndrome - metabolism; Metabolic Syndrome - pathology; Metabolism; Metformin; Metformin - pharmacology; multidisciplinary; Neurodegenerative diseases; Oxidative stress; Oxidative Stress - drug effects; Peroxidation; Protein turnover; Proteins; Rats; Science; Science (multidisciplinary); Signal Transduction - drug effects; Sucrose; Sucrose - metabolism; Superoxide dismutase; β-Amyloid; β-Site APP-cleaving enzyme 1; β-Site APP-cleaving enzymes
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-021-98983-w

Metabolic disturbances are linked to neurodegenerative diseases such as Alzheimer disease (AD). However, the cellular mechanisms underlying this connection are unclear. We evaluated the role of oxidative stress (OS), during early metabolic syndrome (MetS), on amyloidogenic processes in a MetS rat model induced by sucrose. MetS caused OS damage as indicated by serum and hypothalamus lipid peroxidation and elevated serum catalase activity. Tissue catalase and superoxide dismutase activity were unchanged by MetS, but gene expression of nuclear factor erythroid-derived 2-like 2 (NFE2L2), which up-regulates expression of antioxidant enzymes, was higher. Expression of amyloid-β cleaving enzyme 1 (BACE-1) and amyloid precursor protein (APP), key proteins in the amyloidogenesis pathway, were slightly increased by sucrose-intake in the hippocampus and hypothalamus. Activation and expression of protein kinase B (PKB) and AMP-dependent protein kinase (AMPK), pivotal proteins in metabolism and energy signaling, were similarly affected in the hippocampus and hypothalamus of MetS rats. Brain creatine kinase activity decreased in brain tissues from rats with MetS, mainly due to irreversible oxidation. Chronic metformin administration partially reversed oxidative damage in sucrose-fed animals, together with increased AMPK activation; probably by modulating BACE-1 and NFE2L2. AMPK activation may be considered as a preventive therapy for early MetS and associated neurodegenerative diseases.