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

Autor: Clayton A. Whitmore, Justin R. Haynes, William J. Behof, Adam J. Rosenberg, Mohammed N. Tantawy, Brian C. Hachey, Brian E. Wadzinski, Benjamin W. Spiller, Todd E. Peterson, Krista C. Paffenroth, Fiona E. Harrison, Robert B. Beelman, Printha Wijesinghe, Joanne A. Matsubara, Wellington Pham
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Pharmaceuticals, Vol 15, Iss 6, p 742 (2022)
Druh dokumentu: article
ISSN: 1424-8247
DOI: 10.3390/ph15060742
Popis: 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 [11C]PIB, [11C]ERGO, and [18F]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.
Databáze: Directory of Open Access Journals
Nepřihlášeným uživatelům se plný text nezobrazuje