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

Abstract 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 Me...

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Autores principales:	Luz Camacho-Castillo, Bryan V. Phillips-Farfán, Gabriela Rosas-Mendoza, Aidee Baires-López, Danira Toral-Ríos, Victoria Campos-Peña, Karla Carvajal
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/5e27d5d0790145468f3c0c90ab8ce75b
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spelling	oai:doaj.org-article:5e27d5d0790145468f3c0c90ab8ce75b2021-12-02T17:18:20ZIncreased oxidative stress contributes to enhance brain amyloidogenesis and blunts energy metabolism in sucrose-fed rat: effect of AMPK activation10.1038/s41598-021-98983-w2045-2322https://doaj.org/article/5e27d5d0790145468f3c0c90ab8ce75b2021-10-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-98983-whttps://doaj.org/toc/2045-2322Abstract 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.Luz Camacho-CastilloBryan V. Phillips-FarfánGabriela Rosas-MendozaAidee Baires-LópezDanira Toral-RíosVictoria Campos-PeñaKarla CarvajalNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Luz Camacho-Castillo Bryan V. Phillips-Farfán Gabriela Rosas-Mendoza Aidee Baires-López Danira Toral-Ríos Victoria Campos-Peña Karla Carvajal Increased oxidative stress contributes to enhance brain amyloidogenesis and blunts energy metabolism in sucrose-fed rat: effect of AMPK activation
description	Abstract 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.
format	article
author	Luz Camacho-Castillo Bryan V. Phillips-Farfán Gabriela Rosas-Mendoza Aidee Baires-López Danira Toral-Ríos Victoria Campos-Peña Karla Carvajal
author_facet	Luz Camacho-Castillo Bryan V. Phillips-Farfán Gabriela Rosas-Mendoza Aidee Baires-López Danira Toral-Ríos Victoria Campos-Peña Karla Carvajal
author_sort	Luz Camacho-Castillo
title	Increased oxidative stress contributes to enhance brain amyloidogenesis and blunts energy metabolism in sucrose-fed rat: effect of AMPK activation
title_short	Increased oxidative stress contributes to enhance brain amyloidogenesis and blunts energy metabolism in sucrose-fed rat: effect of AMPK activation
title_full	Increased oxidative stress contributes to enhance brain amyloidogenesis and blunts energy metabolism in sucrose-fed rat: effect of AMPK activation
title_fullStr	Increased oxidative stress contributes to enhance brain amyloidogenesis and blunts energy metabolism in sucrose-fed rat: effect of AMPK activation
title_full_unstemmed	Increased oxidative stress contributes to enhance brain amyloidogenesis and blunts energy metabolism in sucrose-fed rat: effect of AMPK activation
title_sort	increased oxidative stress contributes to enhance brain amyloidogenesis and blunts energy metabolism in sucrose-fed rat: effect of ampk activation
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/5e27d5d0790145468f3c0c90ab8ce75b
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Increased oxidative stress contributes to enhance brain amyloidogenesis and blunts energy metabolism in sucrose-fed rat: effect of AMPK activation

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