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Aging and Progression of Beta-Amyloid Pathology in Alzheimer’s Disease Correlates with Microglial Heme-Oxygenase-1 Overexpression

Neuroinflammation and oxidative stress are being recognized as characteristic hallmarks in many neurodegenerative diseases, especially those that portray proteinopathy, such as Alzheimer’s disease (AD). Heme-oxygenase 1 (HO-1) is an inducible enzyme with antioxidant and anti-inflammatory properties,...

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Autores principales: Fernández-Mendívil, Cristina, Arreola, Miguel A., Hohsfield, Lindsay A., Green, Kim N., Lopez, Manuela G.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7402118/
https://www.ncbi.nlm.nih.gov/pubmed/32708329
http://dx.doi.org/10.3390/antiox9070644
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author Fernández-Mendívil, Cristina
Arreola, Miguel A.
Hohsfield, Lindsay A.
Green, Kim N.
Lopez, Manuela G.
author_facet Fernández-Mendívil, Cristina
Arreola, Miguel A.
Hohsfield, Lindsay A.
Green, Kim N.
Lopez, Manuela G.
author_sort Fernández-Mendívil, Cristina
collection PubMed
description Neuroinflammation and oxidative stress are being recognized as characteristic hallmarks in many neurodegenerative diseases, especially those that portray proteinopathy, such as Alzheimer’s disease (AD). Heme-oxygenase 1 (HO-1) is an inducible enzyme with antioxidant and anti-inflammatory properties, while microglia are the immune cells in the central nervous system. To elucidate the brain expression profile of microglial HO-1 in aging and AD-progression, we have used the 5xFAD (five familial AD mutations) mouse model of AD and their littermates at different ages (four, eight, 12, and 18 months). Total brain expression of HO-1 was increased with aging and such increase was even higher in 5xFAD animals. In co-localization studies, HO-1 expression was mainly found in microglia vs. other brain cells. The percentage of microglial cells expressing HO-1 and the amount of HO-1 expressed within microglia increased progressively with aging. Furthermore, this upregulation was increased by 2–3-fold in the elder 5xFAD mice. In addition, microglia overexpressing HO-1 was predominately found surrounding beta-amyloid plaques. These results were corroborated using postmortem brain samples from AD patients, where microglial HO-1 was found up-regulated in comparison to brain samples from aged matched non-demented patients. This study demonstrates that microglial HO-1 expression increases with aging and especially with AD progression, highlighting HO-1 as a potential biomarker or therapeutic target for AD.
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spelling pubmed-74021182020-08-07 Aging and Progression of Beta-Amyloid Pathology in Alzheimer’s Disease Correlates with Microglial Heme-Oxygenase-1 Overexpression Fernández-Mendívil, Cristina Arreola, Miguel A. Hohsfield, Lindsay A. Green, Kim N. Lopez, Manuela G. Antioxidants (Basel) Article Neuroinflammation and oxidative stress are being recognized as characteristic hallmarks in many neurodegenerative diseases, especially those that portray proteinopathy, such as Alzheimer’s disease (AD). Heme-oxygenase 1 (HO-1) is an inducible enzyme with antioxidant and anti-inflammatory properties, while microglia are the immune cells in the central nervous system. To elucidate the brain expression profile of microglial HO-1 in aging and AD-progression, we have used the 5xFAD (five familial AD mutations) mouse model of AD and their littermates at different ages (four, eight, 12, and 18 months). Total brain expression of HO-1 was increased with aging and such increase was even higher in 5xFAD animals. In co-localization studies, HO-1 expression was mainly found in microglia vs. other brain cells. The percentage of microglial cells expressing HO-1 and the amount of HO-1 expressed within microglia increased progressively with aging. Furthermore, this upregulation was increased by 2–3-fold in the elder 5xFAD mice. In addition, microglia overexpressing HO-1 was predominately found surrounding beta-amyloid plaques. These results were corroborated using postmortem brain samples from AD patients, where microglial HO-1 was found up-regulated in comparison to brain samples from aged matched non-demented patients. This study demonstrates that microglial HO-1 expression increases with aging and especially with AD progression, highlighting HO-1 as a potential biomarker or therapeutic target for AD. MDPI 2020-07-21 /pmc/articles/PMC7402118/ /pubmed/32708329 http://dx.doi.org/10.3390/antiox9070644 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Fernández-Mendívil, Cristina
Arreola, Miguel A.
Hohsfield, Lindsay A.
Green, Kim N.
Lopez, Manuela G.
Aging and Progression of Beta-Amyloid Pathology in Alzheimer’s Disease Correlates with Microglial Heme-Oxygenase-1 Overexpression
title Aging and Progression of Beta-Amyloid Pathology in Alzheimer’s Disease Correlates with Microglial Heme-Oxygenase-1 Overexpression
title_full Aging and Progression of Beta-Amyloid Pathology in Alzheimer’s Disease Correlates with Microglial Heme-Oxygenase-1 Overexpression
title_fullStr Aging and Progression of Beta-Amyloid Pathology in Alzheimer’s Disease Correlates with Microglial Heme-Oxygenase-1 Overexpression
title_full_unstemmed Aging and Progression of Beta-Amyloid Pathology in Alzheimer’s Disease Correlates with Microglial Heme-Oxygenase-1 Overexpression
title_short Aging and Progression of Beta-Amyloid Pathology in Alzheimer’s Disease Correlates with Microglial Heme-Oxygenase-1 Overexpression
title_sort aging and progression of beta-amyloid pathology in alzheimer’s disease correlates with microglial heme-oxygenase-1 overexpression
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7402118/
https://www.ncbi.nlm.nih.gov/pubmed/32708329
http://dx.doi.org/10.3390/antiox9070644
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