Oleocanthal Ameliorates Metabolic and Behavioral Phenotypes in a Mouse Model of Alzheimer’s Disease
Aging is a major risk factor for Alzheimer’s disease (AD). AD mouse models are frequently used to assess pathology, behavior, and memory in AD research. While the pathological characteristics of AD are well established, our understanding of the changes in the metabolic phenotypes with age and pathol...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-07-01
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| Series: | Molecules |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1420-3049/28/14/5592 |
| _version_ | 1797588025604046848 |
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| author | Euitaek Yang Junwei Wang Lauren N. Woodie Michael W. Greene Amal Kaddoumi |
| author_facet | Euitaek Yang Junwei Wang Lauren N. Woodie Michael W. Greene Amal Kaddoumi |
| author_sort | Euitaek Yang |
| collection | DOAJ |
| description | Aging is a major risk factor for Alzheimer’s disease (AD). AD mouse models are frequently used to assess pathology, behavior, and memory in AD research. While the pathological characteristics of AD are well established, our understanding of the changes in the metabolic phenotypes with age and pathology is limited. In this work, we used the Promethion cage systems<sup>®</sup> to monitor changes in physiological metabolic and behavioral parameters with age and pathology in wild-type and 5xFAD mouse models. Then, we assessed whether these parameters could be altered by treatment with oleocanthal, a phenolic compound with neuroprotective properties. Findings demonstrated metabolic parameters such as body weight, food and water intake, energy expenditure, dehydration, and respiratory exchange rate, and the behavioral parameters of sleep patterns and anxiety-like behavior are altered by age and pathology. However, the effect of pathology on these parameters was significantly greater than normal aging, which could be linked to amyloid-β deposition and blood–brain barrier (BBB) disruption. In addition, and for the first time, our findings suggest an inverse correlation between sleep hours and BBB breakdown. Treatment with oleocanthal improved the assessed parameters and reduced anxiety-like behavior symptoms and sleep disturbances. In conclusion, aging and AD are associated with metabolism and behavior changes, with the changes being greater with the latter, which were rectified by oleocanthal. In addition, our findings suggest that monitoring changes in metabolic and behavioral phenotypes could provide a valuable tool to assess disease severity and treatment efficacy in AD mouse models. |
| first_indexed | 2024-03-11T00:47:09Z |
| format | Article |
| id | doaj.art-a810e4e65eef46b5a83519cbd35d0792 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-11T00:47:09Z |
| publishDate | 2023-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-a810e4e65eef46b5a83519cbd35d07922023-11-18T20:44:21ZengMDPI AGMolecules1420-30492023-07-012814559210.3390/molecules28145592Oleocanthal Ameliorates Metabolic and Behavioral Phenotypes in a Mouse Model of Alzheimer’s DiseaseEuitaek Yang0Junwei Wang1Lauren N. Woodie2Michael W. Greene3Amal Kaddoumi4Department of Drug Discovery and Development, Harrison College of Pharmacy, Auburn University, 720 S Donahue Dr., Auburn, AL 36849, USADepartment of Drug Discovery and Development, Harrison College of Pharmacy, Auburn University, 720 S Donahue Dr., Auburn, AL 36849, USADepartment of Nutrition, College of Human Sciences, Auburn University, Auburn, AL 36849, USADepartment of Nutrition, College of Human Sciences, Auburn University, Auburn, AL 36849, USADepartment of Drug Discovery and Development, Harrison College of Pharmacy, Auburn University, 720 S Donahue Dr., Auburn, AL 36849, USAAging is a major risk factor for Alzheimer’s disease (AD). AD mouse models are frequently used to assess pathology, behavior, and memory in AD research. While the pathological characteristics of AD are well established, our understanding of the changes in the metabolic phenotypes with age and pathology is limited. In this work, we used the Promethion cage systems<sup>®</sup> to monitor changes in physiological metabolic and behavioral parameters with age and pathology in wild-type and 5xFAD mouse models. Then, we assessed whether these parameters could be altered by treatment with oleocanthal, a phenolic compound with neuroprotective properties. Findings demonstrated metabolic parameters such as body weight, food and water intake, energy expenditure, dehydration, and respiratory exchange rate, and the behavioral parameters of sleep patterns and anxiety-like behavior are altered by age and pathology. However, the effect of pathology on these parameters was significantly greater than normal aging, which could be linked to amyloid-β deposition and blood–brain barrier (BBB) disruption. In addition, and for the first time, our findings suggest an inverse correlation between sleep hours and BBB breakdown. Treatment with oleocanthal improved the assessed parameters and reduced anxiety-like behavior symptoms and sleep disturbances. In conclusion, aging and AD are associated with metabolism and behavior changes, with the changes being greater with the latter, which were rectified by oleocanthal. In addition, our findings suggest that monitoring changes in metabolic and behavioral phenotypes could provide a valuable tool to assess disease severity and treatment efficacy in AD mouse models.https://www.mdpi.com/1420-3049/28/14/5592Alzheimer’s diseaseblood–brain barriermetabolic phenotypesleep behaviorPromethion cagesoleocanthal |
| spellingShingle | Euitaek Yang Junwei Wang Lauren N. Woodie Michael W. Greene Amal Kaddoumi Oleocanthal Ameliorates Metabolic and Behavioral Phenotypes in a Mouse Model of Alzheimer’s Disease Molecules Alzheimer’s disease blood–brain barrier metabolic phenotype sleep behavior Promethion cages oleocanthal |
| title | Oleocanthal Ameliorates Metabolic and Behavioral Phenotypes in a Mouse Model of Alzheimer’s Disease |
| title_full | Oleocanthal Ameliorates Metabolic and Behavioral Phenotypes in a Mouse Model of Alzheimer’s Disease |
| title_fullStr | Oleocanthal Ameliorates Metabolic and Behavioral Phenotypes in a Mouse Model of Alzheimer’s Disease |
| title_full_unstemmed | Oleocanthal Ameliorates Metabolic and Behavioral Phenotypes in a Mouse Model of Alzheimer’s Disease |
| title_short | Oleocanthal Ameliorates Metabolic and Behavioral Phenotypes in a Mouse Model of Alzheimer’s Disease |
| title_sort | oleocanthal ameliorates metabolic and behavioral phenotypes in a mouse model of alzheimer s disease |
| topic | Alzheimer’s disease blood–brain barrier metabolic phenotype sleep behavior Promethion cages oleocanthal |
| url | https://www.mdpi.com/1420-3049/28/14/5592 |
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