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Longitudinal Consumption of Ergothioneine Reduces Oxidative Stress and Amyloid Plaques and Restores Glucose Metabolism in the 5XFAD Mouse Model of Alzheimer’s Disease

Background: Ergothioneine (ERGO) is a unique antioxidant and a rare amino acid available in fungi and various bacteria but not in higher plants or animals. Substantial research data indicate that ERGO is a physiological antioxidant cytoprotectant. Different from other antioxidants that need to breac...

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Autores principales: Whitmore, Clayton A., Haynes, Justin R., Behof, William J., Rosenberg, Adam J., Tantawy, Mohammed N., Hachey, Brian C., Wadzinski, Brian E., Spiller, Benjamin W., Peterson, Todd E., Paffenroth, Krista C., Harrison, Fiona E., Beelman, Robert B., Wijesinghe, Printha, Matsubara, Joanne A., Pham, Wellington
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9228400/
https://www.ncbi.nlm.nih.gov/pubmed/35745661
http://dx.doi.org/10.3390/ph15060742
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author Whitmore, Clayton A.
Haynes, Justin R.
Behof, William J.
Rosenberg, Adam J.
Tantawy, Mohammed N.
Hachey, Brian C.
Wadzinski, Brian E.
Spiller, Benjamin W.
Peterson, Todd E.
Paffenroth, Krista C.
Harrison, Fiona E.
Beelman, Robert B.
Wijesinghe, Printha
Matsubara, Joanne A.
Pham, Wellington
author_facet Whitmore, Clayton A.
Haynes, Justin R.
Behof, William J.
Rosenberg, Adam J.
Tantawy, Mohammed N.
Hachey, Brian C.
Wadzinski, Brian E.
Spiller, Benjamin W.
Peterson, Todd E.
Paffenroth, Krista C.
Harrison, Fiona E.
Beelman, Robert B.
Wijesinghe, Printha
Matsubara, Joanne A.
Pham, Wellington
author_sort Whitmore, Clayton A.
collection PubMed
description Background: Ergothioneine (ERGO) is a unique antioxidant and a rare amino acid available in fungi and various bacteria but not in higher plants or animals. Substantial research data indicate that ERGO is a physiological antioxidant cytoprotectant. Different from other antioxidants that need to breach the blood–brain barrier to enter the brain parenchyma, a specialized transporter called OCTN1 has been identified for transporting ERGO to the brain. Purpose: To assess whether consumption of ERGO can prevent the progress of Alzheimer’s disease (AD) on young (4-month-old) 5XFAD mice. Methods and materials: Three cohorts of mice were tested in this study, including ERGO-treated 5XFAD, non-treated 5XFAD, and WT mice. After the therapy, the animals went through various behavioral experiments to assess cognition. Then, mice were scanned with PET imaging to evaluate the biomarkers associated with AD using [(11)C]PIB, [(11)C]ERGO, and [(18)F]FDG radioligands. At the end of imaging, the animals went through cardiac perfusion, and the brains were isolated for immunohistology. Results: Young (4-month-old) 5XFAD mice did not show a cognitive deficit, and thus, we observed modest improvement in the treated counterparts. In contrast, the response to therapy was clearly detected at the molecular level. Treating 5XFAD mice with ERGO resulted in reduced amyloid plaques, oxidative stress, and rescued glucose metabolism. Conclusions: Consumption of high amounts of ERGO benefits the brain. ERGO has the potential to prevent AD. This work also demonstrates the power of imaging technology to assess response during therapy.
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spelling pubmed-92284002022-06-25 Longitudinal Consumption of Ergothioneine Reduces Oxidative Stress and Amyloid Plaques and Restores Glucose Metabolism in the 5XFAD Mouse Model of Alzheimer’s Disease Whitmore, Clayton A. Haynes, Justin R. Behof, William J. Rosenberg, Adam J. Tantawy, Mohammed N. Hachey, Brian C. Wadzinski, Brian E. Spiller, Benjamin W. Peterson, Todd E. Paffenroth, Krista C. Harrison, Fiona E. Beelman, Robert B. Wijesinghe, Printha Matsubara, Joanne A. Pham, Wellington Pharmaceuticals (Basel) Article Background: Ergothioneine (ERGO) is a unique antioxidant and a rare amino acid available in fungi and various bacteria but not in higher plants or animals. Substantial research data indicate that ERGO is a physiological antioxidant cytoprotectant. Different from other antioxidants that need to breach the blood–brain barrier to enter the brain parenchyma, a specialized transporter called OCTN1 has been identified for transporting ERGO to the brain. Purpose: To assess whether consumption of ERGO can prevent the progress of Alzheimer’s disease (AD) on young (4-month-old) 5XFAD mice. Methods and materials: Three cohorts of mice were tested in this study, including ERGO-treated 5XFAD, non-treated 5XFAD, and WT mice. After the therapy, the animals went through various behavioral experiments to assess cognition. Then, mice were scanned with PET imaging to evaluate the biomarkers associated with AD using [(11)C]PIB, [(11)C]ERGO, and [(18)F]FDG radioligands. At the end of imaging, the animals went through cardiac perfusion, and the brains were isolated for immunohistology. Results: Young (4-month-old) 5XFAD mice did not show a cognitive deficit, and thus, we observed modest improvement in the treated counterparts. In contrast, the response to therapy was clearly detected at the molecular level. Treating 5XFAD mice with ERGO resulted in reduced amyloid plaques, oxidative stress, and rescued glucose metabolism. Conclusions: Consumption of high amounts of ERGO benefits the brain. ERGO has the potential to prevent AD. This work also demonstrates the power of imaging technology to assess response during therapy. MDPI 2022-06-13 /pmc/articles/PMC9228400/ /pubmed/35745661 http://dx.doi.org/10.3390/ph15060742 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Whitmore, Clayton A.
Haynes, Justin R.
Behof, William J.
Rosenberg, Adam J.
Tantawy, Mohammed N.
Hachey, Brian C.
Wadzinski, Brian E.
Spiller, Benjamin W.
Peterson, Todd E.
Paffenroth, Krista C.
Harrison, Fiona E.
Beelman, Robert B.
Wijesinghe, Printha
Matsubara, Joanne A.
Pham, Wellington
Longitudinal Consumption of Ergothioneine Reduces Oxidative Stress and Amyloid Plaques and Restores Glucose Metabolism in the 5XFAD Mouse Model of Alzheimer’s Disease
title Longitudinal Consumption of Ergothioneine Reduces Oxidative Stress and Amyloid Plaques and Restores Glucose Metabolism in the 5XFAD Mouse Model of Alzheimer’s Disease
title_full Longitudinal Consumption of Ergothioneine Reduces Oxidative Stress and Amyloid Plaques and Restores Glucose Metabolism in the 5XFAD Mouse Model of Alzheimer’s Disease
title_fullStr Longitudinal Consumption of Ergothioneine Reduces Oxidative Stress and Amyloid Plaques and Restores Glucose Metabolism in the 5XFAD Mouse Model of Alzheimer’s Disease
title_full_unstemmed Longitudinal Consumption of Ergothioneine Reduces Oxidative Stress and Amyloid Plaques and Restores Glucose Metabolism in the 5XFAD Mouse Model of Alzheimer’s Disease
title_short Longitudinal Consumption of Ergothioneine Reduces Oxidative Stress and Amyloid Plaques and Restores Glucose Metabolism in the 5XFAD Mouse Model of Alzheimer’s Disease
title_sort longitudinal consumption of ergothioneine reduces oxidative stress and amyloid plaques and restores glucose metabolism in the 5xfad mouse model of alzheimer’s disease
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9228400/
https://www.ncbi.nlm.nih.gov/pubmed/35745661
http://dx.doi.org/10.3390/ph15060742
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