Longitudinal Consumption of Ergothioneine Reduces Oxidative Stress and Amyloid Plaques and Restores Glucose Metabolism in the 5XFAD Mouse Model of Alzheimer’s Disease
<i>Background:</i> 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...
| Main Authors: | , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-06-01
|
| Series: | Pharmaceuticals |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1424-8247/15/6/742 |
| _version_ | 1797483408703619072 |
|---|---|
| author | 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 |
| author_facet | 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 |
| author_sort | Clayton A. Whitmore |
| collection | DOAJ |
| description | <i>Background:</i> 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. <i>Purpose</i>: To assess whether consumption of ERGO can prevent the progress of Alzheimer’s disease (AD) on young (4-month-old) 5XFAD mice. <i>Methods and materials</i>: 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 [<sup>11</sup>C]PIB, [<sup>11</sup>C]ERGO, and [<sup>18</sup>F]FDG radioligands. At the end of imaging, the animals went through cardiac perfusion, and the brains were isolated for immunohistology. <i>Results</i>: 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. <i>Conclusions</i>: 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. |
| first_indexed | 2024-03-09T22:46:34Z |
| format | Article |
| id | doaj.art-882ef7134def4279bbf43586617325cc |
| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-09T22:46:34Z |
| publishDate | 2022-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-882ef7134def4279bbf43586617325cc2023-11-23T18:27:57ZengMDPI AGPharmaceuticals1424-82472022-06-0115674210.3390/ph15060742Longitudinal Consumption of Ergothioneine Reduces Oxidative Stress and Amyloid Plaques and Restores Glucose Metabolism in the 5XFAD Mouse Model of Alzheimer’s DiseaseClayton A. Whitmore0Justin R. Haynes1William J. Behof2Adam J. Rosenberg3Mohammed N. Tantawy4Brian C. Hachey5Brian E. Wadzinski6Benjamin W. Spiller7Todd E. Peterson8Krista C. Paffenroth9Fiona E. Harrison10Robert B. Beelman11Printha Wijesinghe12Joanne A. Matsubara13Wellington Pham14Vanderbilt University Institute of Imaging Science, Vanderbilt University Medical Center, Nashville, TN 37232, USAVanderbilt University Institute of Imaging Science, Vanderbilt University Medical Center, Nashville, TN 37232, USAVanderbilt University Institute of Imaging Science, Vanderbilt University Medical Center, Nashville, TN 37232, USAVanderbilt University Institute of Imaging Science, Vanderbilt University Medical Center, Nashville, TN 37232, USAVanderbilt University Institute of Imaging Science, Vanderbilt University Medical Center, Nashville, TN 37232, USADepartment of Biochemistry, Vanderbilt University, Nashville, TN 37232, USADepartment of Pharmacology, Vanderbilt University, Nashville, TN 37233, USADepartment of Pharmacology, Vanderbilt University, Nashville, TN 37233, USAVanderbilt University Institute of Imaging Science, Vanderbilt University Medical Center, Nashville, TN 37232, USADepartment of Pharmacology, Vanderbilt University, Nashville, TN 37233, USAVanderbilt Brain Institute, Vanderbilt University, Nashville, TN 37232, USADepartment of Food Science, Center for Plant and Mushroom Foods for Health, Penn State University, University Park, PA 16802, USADepartment of Ophthalmology and Visual Sciences, University of British Columbia, Vancouver, BC V5Z 3N9, CanadaDepartment of Ophthalmology and Visual Sciences, University of British Columbia, Vancouver, BC V5Z 3N9, CanadaVanderbilt University Institute of Imaging Science, Vanderbilt University Medical Center, Nashville, TN 37232, USA<i>Background:</i> 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. <i>Purpose</i>: To assess whether consumption of ERGO can prevent the progress of Alzheimer’s disease (AD) on young (4-month-old) 5XFAD mice. <i>Methods and materials</i>: 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 [<sup>11</sup>C]PIB, [<sup>11</sup>C]ERGO, and [<sup>18</sup>F]FDG radioligands. At the end of imaging, the animals went through cardiac perfusion, and the brains were isolated for immunohistology. <i>Results</i>: 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. <i>Conclusions</i>: 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.https://www.mdpi.com/1424-8247/15/6/742ergothioneineROSPETAlzheimeroxidative stress5XFAD |
| spellingShingle | 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 Longitudinal Consumption of Ergothioneine Reduces Oxidative Stress and Amyloid Plaques and Restores Glucose Metabolism in the 5XFAD Mouse Model of Alzheimer’s Disease Pharmaceuticals ergothioneine ROS PET Alzheimer oxidative stress 5XFAD |
| 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 | ergothioneine ROS PET Alzheimer oxidative stress 5XFAD |
| url | https://www.mdpi.com/1424-8247/15/6/742 |
| work_keys_str_mv | AT claytonawhitmore longitudinalconsumptionofergothioneinereducesoxidativestressandamyloidplaquesandrestoresglucosemetabolisminthe5xfadmousemodelofalzheimersdisease AT justinrhaynes longitudinalconsumptionofergothioneinereducesoxidativestressandamyloidplaquesandrestoresglucosemetabolisminthe5xfadmousemodelofalzheimersdisease AT williamjbehof longitudinalconsumptionofergothioneinereducesoxidativestressandamyloidplaquesandrestoresglucosemetabolisminthe5xfadmousemodelofalzheimersdisease AT adamjrosenberg longitudinalconsumptionofergothioneinereducesoxidativestressandamyloidplaquesandrestoresglucosemetabolisminthe5xfadmousemodelofalzheimersdisease AT mohammedntantawy longitudinalconsumptionofergothioneinereducesoxidativestressandamyloidplaquesandrestoresglucosemetabolisminthe5xfadmousemodelofalzheimersdisease AT brianchachey longitudinalconsumptionofergothioneinereducesoxidativestressandamyloidplaquesandrestoresglucosemetabolisminthe5xfadmousemodelofalzheimersdisease AT brianewadzinski longitudinalconsumptionofergothioneinereducesoxidativestressandamyloidplaquesandrestoresglucosemetabolisminthe5xfadmousemodelofalzheimersdisease AT benjaminwspiller longitudinalconsumptionofergothioneinereducesoxidativestressandamyloidplaquesandrestoresglucosemetabolisminthe5xfadmousemodelofalzheimersdisease AT toddepeterson longitudinalconsumptionofergothioneinereducesoxidativestressandamyloidplaquesandrestoresglucosemetabolisminthe5xfadmousemodelofalzheimersdisease AT kristacpaffenroth longitudinalconsumptionofergothioneinereducesoxidativestressandamyloidplaquesandrestoresglucosemetabolisminthe5xfadmousemodelofalzheimersdisease AT fionaeharrison longitudinalconsumptionofergothioneinereducesoxidativestressandamyloidplaquesandrestoresglucosemetabolisminthe5xfadmousemodelofalzheimersdisease AT robertbbeelman longitudinalconsumptionofergothioneinereducesoxidativestressandamyloidplaquesandrestoresglucosemetabolisminthe5xfadmousemodelofalzheimersdisease AT printhawijesinghe longitudinalconsumptionofergothioneinereducesoxidativestressandamyloidplaquesandrestoresglucosemetabolisminthe5xfadmousemodelofalzheimersdisease AT joanneamatsubara longitudinalconsumptionofergothioneinereducesoxidativestressandamyloidplaquesandrestoresglucosemetabolisminthe5xfadmousemodelofalzheimersdisease AT wellingtonpham longitudinalconsumptionofergothioneinereducesoxidativestressandamyloidplaquesandrestoresglucosemetabolisminthe5xfadmousemodelofalzheimersdisease |